US20100068278A1 - Ex vivo modifiable medicament release-associations - Google Patents

Abstract

Described embodiments include a final dosage form, an article of manufacture, and method. A described final dosage form includes a medicament, and a substance associated with the medicament in a first release-control state. In the first release-control state, the medicament has a first bioavailability to the animal. The substance is modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state, wherein the medicament has a second bioavailability to the animal. The final dosage form also includes another medicament, and another substance associated with the another medicament in another first release-control state. In the another first release-control state, the another medicament has another first bioavailability to the animal. The another substance is modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state, wherein the another medicament has another second bioavailability.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
• The present application is related to and claims the benefit of the earliest available effective filing date(s) from the following listed application(s) (the “Related Applications”) (e.g., claims earliest available priority dates for other than provisional patent applications or claims benefits under 35 USC §119(e) for provisional patent applications, for any and all parent, grandparent, great-grandparent, etc. applications of the Related Application(s)).
RELATED APPLICATIONS
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. 12/284,015, titled INDIVIDUALIZABLE DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Sep. 16, 2008, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. 12/284,014, titled PERSONALIZABLE DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Sep. 16, 2008, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. 12/284,013, titled MODIFIABLE DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Sep. 16, 2008, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. 12/322,877, titled EX VIVO-MODIFIABLE PARTICLE OR POLYMERIC BASED FINAL DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Feb. 5, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. 12/322,874, titled MODIFYING A MEDICAMENT AVAILABLILITY STATE OF A FINAL DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Feb. 5, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. 12/322,878, titled EX VIVO ACTIVATABLE DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Feb. 5, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. To be assigned, titled EX VIVO MODIFIABLE PARTICLE OR POLYMERIC MEDICAMENT CARRIER, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. To be assigned, titled EX VIVO-MODIFIABLE MULTIPLE-RELEASE STATE FINAL DOSAGE FORM medicament carrier, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. To be assigned, titled SYSTEM FOR EX VIVO MODIFICATION OF MEDICAMENT RELEASE STATE, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. To be assigned, titled MULTIPLE CHAMBER EX VIVO ADJUSTABLE-RELEASE FINAL DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. To be assigned, titled EX VIVO MODIFIABLE MULTIPLE MEDICAMENT FINAL DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. To be assigned, titled EX VIVO MODIFIABLE MEDICAMENT RELEASE-SITES FINAL DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• For purposes of the USPTO extra-statutory requirements, the present application constitutes a continuation-in-part of U.S. patent application Ser. No. To be assigned, titled EX VIVO MODIFIABLE MEDICAMENT RELEASE-SUBSTANCE, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which is currently co-pending, or is an application of which a currently co-pending application is entitled to the benefit of the filing date.
• The United States Patent Office (USPTO) has published a notice to the effect that the USPTO's computer programs require that patent applicants reference both a serial number and indicate whether an application is a continuation or continuation-in-part. Stephen G. Kunin,Benefit of Prior-Filed Application,USPTO Official Gazette Mar. 18, 2003, available at http://www.uspto.gov/web/offices/com/sol/og/2003/week11/patbene.htm. The present Applicant Entity (hereinafter “Applicant”) has provided above a specific reference to the application(s) from which priority is being claimed as recited by statute. Applicant understands that the statute is unambiguous in its specific reference language and does not require either a serial number or any characterization, such as “continuation” or “continuation-in-part,” for claiming priority to U.S. patent applications. Notwithstanding the foregoing, Applicant understands that the USPTO's computer programs have certain data entry requirements, and hence Applicant is designating the present application as a continuation-in-part of its parent applications as set forth above, but expressly points out that such designations are not to be construed in any way as any type of commentary or admission as to whether or not the present application contains any new matter in addition to the matter of its parent application(s).
• All subject matter of the Related Applications and of any and all parent, grandparent, great-grandparent, etc. applications of the Related Applications is incorporated herein by reference to the extent such subject matter is not inconsistent herewith.
SUMMARY
• An embodiment of the subject matter described herein describes a final dosage form for administering medicament to an animal. The final dosage form includes a medicament, and a substance associated with the medicament in a first release-control state. In the first release-control state, the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The substance is modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. The final dosage form also includes another medicament, and another substance associated with the another medicament in another first release-control state. In the another first release-control state, the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal. The another substance is modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal.
• An embodiment of the subject matter described herein describes a final dosage form for administering medicament to an animal. The final dosage form includes a medicament, and a substance associated with the medicament in a first state. In the first state, the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The substance is modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second state, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. The final dosage form also includes another medicament, and another substance associated with the another medicament in another first state. In the another first state, the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal. The another substance is modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second state, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal.
• An embodiment of the subject matter described herein describes a method of modifying bioavailability of medicament described by a final dosage form for administering medicament to an animal. The final dosage form includes a medicament, and a substance associated with the medicament in a first release-control state. In the first release-control state, the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The substance is modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. The final dosage form also includes another medicament, and another substance associated with the another medicament in another first release-control state. In the another first release-control state, the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal. The another substance is modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal. The method includes transforming the final dosage form into a selected medicament release state by initiating an ex vivo exposure of the substance associated with the medicament in a first release-control state or an ex vivo exposure of the another substance associated with the another medicament in another first release-control state to a modification stimulus respectfully selected from the stimulus or the another stimulus. In an embodiment, the method may include receiving a signal indicative of a chosen medicament bioavailability of the final dosage form. In an embodiment, the method may include selecting the medicament-release state of the substance associated with the medicament or of the another substance associated with the another medicament in response to the chosen medicament-bioavailability of the final dosage form. In an embodiment, the method may include selecting the modification stimulus from the stimulus or the another stimulus in response to the selected medicament-release state.
• An embodiment of the subject matter described herein describes an article of manufacture for administering medicament to an animal. The article includes a medicament. The article also includes an intelligent molecular means associated with the medicament in a first release-control state, wherein the medicament has a first bioavailability to the animal if the article of manufacture is administered to the animal. The intelligent molecular means is modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state, wherein the medicament has a second bioavailability to the animal if the article of manufacture is administered to the animal. The article includes another medicament. The article also includes another intelligent molecular means associated with the another medicament in another first release-control state, wherein the another medicament has another first bioavailability to the animal if the article of manufacture is administered to the animal. The another intelligent molecular means is modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state, wherein the another medicament has another second bioavailability to the animal if the article of manufacture is administered to the animal.
• The foregoing summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features will become apparent by reference to the drawings and the following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 illustrates an example environment that includes an animal, a cross-sectional view of an example final dosage form for administering a medicament to the animal, and an example stimulation source operable to emit a stimulus;
• FIG. 2 illustrates another example environment that includes the animal, a cross-sectional view of an example final dosage form for administering a medicament to the animal, and the example stimulation source operable to emit the stimulus;
• FIG. 3 illustrates a further example environment that includes the animal, a cross-sectional view of an example final dosage form for administering a medicament to the animal, and the example stimulation source operable to emit the stimulus;
• FIG. 4 illustrates another example environment that includes the animal, a cross-sectional view of an example final dosage form for administering a medicament to the animal, and the example stimulation source operable to emit the stimulus;
• FIG. 5 illustrates a further example environment that includes an animal, a cross-sectional view of an example final dosage form for transporting medicament to the animal;
• FIG. 6 illustrates an example environment that includes an article of manufacture;
• FIG. 7 illustrates an example operational flow modulating a medicament-release characteristic of a final dosage form;
• FIG. 8 illustrates an alternative embodiment of the operational flow ofFIG. 7;
• FIG. 9 illustrates an example operational flow fulfilling a request specifying a dose of a medicament for an individual animal;
• FIG. 10 illustrates an alternative embodiment of the example operational flow ofFIG. 9;
• FIG. 11 illustrates another alternative embodiment of the example operational flow ofFIG. 9
• FIG. 12 illustrates a further embodiment of the example operation ofFIG. 9;
• FIG. 13 illustrates another embodiment of the example operational flow ofFIG. 9;
• FIG. 14 illustrates a further embodiment of the example operational flow ofFIG. 9.
• FIG. 15 illustrates an example environment that includes an animal, a cross-sectional view of an example final dosage form for administering the medicament to the animal, and the example stimulation source operable to emit a stimulus;
• FIG. 16 illustrates an example environment that illustrates a final dosage form having a release element implemented by a characteristic response of a particle or a polymer to the stimulus;
• FIG. 17 illustrates an example environment that includes an article;
• FIG. 18 illustrates an example operational flow modifying a medicament availability characteristic of a final dosage form;
• FIG. 19 illustrates an example final dosage form for administering a medicament to an animal;
• FIG. 20 illustrates an example environment that includes afinal dosage form1502 configurable to administer a medicament to an animal;
• FIG. 21 illustrates an example environment depicting retention and release states of particle or polymeric material (depicted as a hydrogel) responsive to an ex vivo stimulus;
• FIG. 22 illustrates an example environment that includes an article of manufacture;
• FIG. 23 illustrates an example environment that includes a final dosage form for administering the medicament to an animal;
• FIG. 24 illustrates an example environment that includes a final dosage form and an operational flow;
• FIG. 25 illustrates alternative embodiments of the activation operation ofFIG. 24;
• FIG. 26 illustrates an example embodiment of a final dosage form for administering a medicament;
• FIG. 27 illustrates an example system in which embodiments may be implemented;
• FIG. 28 illustrates an example environment that includes a final dosage form for administering the medicament to an animal;
• FIG. 29 illustrates an example environment that includes a final dosage form for administering the medicament to an animal;
• FIG. 30 illustrates an example environment that includes a final dosage form and an operational flow;
• FIG. 31 illustrates an example article of manufacture for administering medicament to an animal;
• FIG. 32 illustrates an example environment that includes a final dosage form for administering medicament to an animal;
• FIG. 33 illustrates an example environment that includes an article of manufacture;
• FIG. 34 illustrates an example environment that includes a final dosage form and an operational flow;
• FIG. 35 illustrates an alternative embodiment of the individualization operation ofFIG. 34;
• FIG. 36 illustrates an alternative embodiment of the individualization operation ofFIG. 34;
• FIG. 37 illustrates an alternative embodiment of the operational flow ofFIG. 34;
• FIG. 38 illustrates an example environment that includes a final dosage form and an operational flow;
• FIG. 39 illustrates an example vehicle for administering a medicament to an animal;
• FIG. 40 illustrates an example system;
• FIG. 41 illustrates an example environment;
• FIG. 42 illustrates an example environment that includes a final dosage form for administering medicament to an animal;
• FIG. 43 illustrates an example environment that includes a final dosage form and an operational flow;
• FIG. 44 illustrates an alternative embodiment of the operational flow ofFIG. 43;
• FIG. 45 illustrates an example environment that includes an article of manufacture;
• FIG. 46 illustrates an example article of manufacture for administering medicament to an animal;
• FIG. 47 illustrates an environment that includes a final dosage form for administering medicament to an animal;
• FIG. 48 illustrates an example environment that includes a final dosage form for administering medicament to an animal;
• FIG. 49 illustrates an example environment that includes a final dosage form and an operational flow;
• FIG. 50 illustrates an example alternative embodiment of the operational flow ofFIG. 49;
• FIG. 51 illustrates an example environment that includes an article ofmanufacture4001;
• FIG. 52 illustrates an example environment that includes an article of manufacture;
• FIG. 53 illustrates an example article of manufacture for administering medicament to an animal;
• FIG. 54 illustrates an example environment that includes a final dosage form for administering medicament to an animal;
• FIG. 55 illustrates an example environment that includes a final dosage form and an operational flow;
• FIG. 56 illustrates an alternative embodiment of the operational flow described inFIG. 55;
• FIG. 57 illustrates an example environment;
• FIG. 58 illustrates an example article of manufacture for administering medicament to an animal;
• FIG. 59 illustrates an example environment that includes a final dosage form for administering medicament to an animal;
• FIG. 60 illustrates an example environment that includes a final dosage form for administering medicament to an animal and an operational flow;
• FIG. 61 illustrates an alternative embodiment of the operational flow described in conjunction withFIG. 60;
• FIG. 62 illustrates an example article of manufacture for administering medicament to an animal;
• FIG. 63 illustrates an example environment that includes a final dosage form for administering medicament to an animal;
• FIG. 64 illustrates an example environment that includes a final dosage form for administering medicament to an animal;
• FIG. 65 illustrates an example environment that includes a final dosage form and an operational flow;
• FIG. 66 illustrates an alternative embodiment of the operational flow described in conjunction withFIG. 65; and
• FIG. 67 illustrates an example article of manufacture for administering medicament to an animal.
DETAILED DESCRIPTION
• In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrated embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here.
• FIG. 1 illustrates anenvironment100 that includes ananimal198, a cross-sectional view of an examplefinal dosage form102 for administering themedicament190 to an animal, such as theanimal198, and anexample stimulus source194 configured to emit astimulus192. In an embodiment, the final dosage form includes a dosage form having completed a manufacturing or production process. In an embodiment, the final dosage form includes a product, finished tablet, or capsule ready for distribution to a hospital, pharmacy, or retail store for individualizing to a particular animal, such as theanimal198. In an embodiment, the final dosage form includes a tablet shape, a spherical shape, or an ellipsoidal shape. In an embodiment, the final dosage form includes a structure or a particle carryable or transportable by a liquid or other fluid carrier.
• In an embodiment, theanimal198 includes any living being capable of voluntary movement and possessing specialized sense organs. In an embodiment, the animal includes a human. In an embodiment, the animal includes a mammal. In an embodiment, administering, administration, or administer the medicament to the animal includes give or apply themedicament190 to the animal. In an embodiment, administering the medicament to the animal includes dispensing the medicament to the animal. In an embodiment, administering the medicament to the animal includes delivering the medicament to the animal. In an embodiment, administering the medicament to the animal includes directly or indirectly injecting the medicament to the animal. In an embodiment, administering the medicament to the animal includes applying the medicament to the animal. In an embodiment, administering the medicament to the animal includes providing the medicament to the animal.
• Thefinal dosage form102 includes anouter layer110, arelease element130, and achamber120. Therelease element130 is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a stimulus. For example, the stimulus may include thestimulus192. Thechamber120 includes achamber wall122, which is substantially within theouter layer110, and is configured to carry themedicament190. In an embodiment, thefinal dosage form102 includes an intermediate outer layer (not shown) with the release element interposed between the outer layer and the intermediate outer layer, and the chamber is substantially within the intermediate outer layer (not shown).
• In an embodiment, theouter layer110 of thefinal dosage form102 includes an outer layer of at least one of a tablet, capsule, particle, or solid final dosage form. In an embodiment, theouter layer110 includes an outer peripheral layer.FIG. 1 illustrates an example embodiment where theouter layer110 includes an outer layer around thechamber wall122 and therelease element130. In an embodiment, theouter layer110 is configured for administration to theanimal198 by at least one of an oral, enteral, inhalation, or implant route. In an embodiment, an enteral route includes a rectal route, or a vaginal route, such as by a suppository. In an embodiment, the outer layer is configured for administration to the animal by at least one of parenteral, nasal, auditory canal, pulmonary, topical, or subdermal route.
• In an embodiment, theouter layer110 includes an outer layer configured to release the medicament in an in vivo environment of the animal. In an embodiment, theouter layer110 includes an outer surface. In an embodiment, the outer layer includes an outer surface of a biocompatible medicament administration vehicle or transport.
• In an embodiment, theouter layer110 of thefinal dosage form102 includes an erodible outer layer. Formulations of erodible dosage forms are known in the art. In an embodiment, the erodible outer layer includes an erodible outer layer that is at least one of soluble, permeable, or disintegrable within theanimal198. In an embodiment, the erodible outer layer includes an erodible outer layer having at least a portion that is at least one of soluble, permeable, or disintegrable in response to an acidic environment within the animal. In an embodiment, the erodible outer layer includes an erodible outer layer having at least a portion that is at least one of soluble, permeable, or disintegrable in response to a pH neutral or a basic environment within the animal.
• In an embodiment, theouter layer110 of thefinal dosage form102 includes an outer portion of a plurality of particles. Examples of such a particle include one or more of hydrogels, microspheres, polymeric microspheres, and nanoparticles as described in Lin et al.,Hydrogels in controlled release formulations: Network design and mathematical modeling,ADVANCEDDRUGDELIVERYREVIEWS58 (2006) (1379-1408). In an embodiment, theouter layer110 of thefinal dosage form102 includes an outer portion of an aggregation of molecules. An embodiment includes anouter layer110 configured to allow an in vivo discharge of at least a portion of themedicament190 from thechamber120 after an exposure of therelease element130 to thestimulus192. An embodiment includes anouter layer110 configured in cooperation with therelease element130 to allow an in vivo discharge of at least a portion of themedicament190 from thechamber120 after an exposure of therelease element130 to the stimulus. In an embodiment, theouter layer110 includes an outer layer of at least a portion of the release element. In an embodiment, the release element forms the outer layer. An embodiment includes an outer layer configured to contain the medicament until the final dosage form is administered into the animal.
• In an embodiment of therelease element130, the first medicament-release state is configured to retard medicament release in vivo and the second medicament-release state is configured to allow medicament release in vivo. In an embodiment of therelease element130, the first medicament-release state is configured to allow medicament release in vivo and the second medicament-release state is configured to retard medicament release in vivo.
• FIG. 1 illustrates arelease element130 disposed within theouter layer110. In an embodiment, the release element includes a release element that is at least partially disposed within the outer layer, or a release element that is not disposed within the outer layer. For example,FIG. 2 infra, illustrates an example of afinal dosage form202 that includes arelease element230 that is not disposed within theouter layer210.FIG. 3, infra, illustrates an example of afinal dosage form302 that includes arelease element330 disposed at least partially within theouter layer310.
• Returning toFIG. 1, in an embodiment, arelease element130 may be configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to thestimulus192. An embodiment includes a release element configured in a first medicament-release state and reconfigurable to a second medicament-release state by an exposure to the stimulus.
• In an embodiment, therelease element130 includes a release element configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a non-ionizing radiation, illustrated as thestimulus192. In an embodiment, therelease element130 is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to an electromagnetic radiation, illustrated as thestimulus192. In an embodiment, therelease element130 is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a light radiation, also illustrated as thestimulus192. For example, light radiation may include at least one of the spectrum of ultraviolet (UV), visible light, /or infrared (IR).
• In an embodiment, therelease element130 includes, but is not limited to, at least one of a poly(vinyl alcohol), gel, gel matrix, hydrogel, or azopolymer membrane. For example, a poly(vinyl alcohol) is described in (S. P. Vijayalakshmi, et al.,Photodegradation of poly(vinyl alcohol)under UV and pulsed-laser irradiation in aqueous solution,JOURNAL OFAPPLIEDPOLYMERSCIENCE, Vol. 102, No. 2, 958-966, 2006). For example, photo responsive polymers, including using an azopolymer with laser holography to generate the gated layer, are described in (J. Kyoo Lee, et. al.,Photo-Triggering of the Membrane Gates in Photo-Responsive Polymer for Drug Release,ENGINEERING INMEDICINE ANDBIOLOGYSOCIETY, (27th Annual International Conference) 2005 Pages:5069-5072 (2005). In an embodiment, the release element includes a photo-labile bond between a molecule of themedicament190 and a bioactivity inhibiting molecule that is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure of the labile bond to the stimulus. Examples of such a photo-labile bond are described in M. Scwarcznski, et al.,Development of first photo responsive prodrug of paclitaxel,16 BIOORGANIC& MEDICALCHEMISTRYLETTERS, Issue 17 4492-4496 (September 2006): Epub 27 June 2006. Scwarcznski, et al., describe synthesization of a prodrug of paclitaxel which has a coumarin derivative conjugated to the amino acid moiety of isotaxel (O-acyl isoform of paclitaxel). The prodrug was selectively converted to isotaxel by visible light irradiation (430 nm) with the cleavage of coumarin. Finally, paclitaxel was released by subsequent spontaneous O—N intramolecular acyl migration.
• In addition, the release element may include at least one of an additional appropriate photodegradable /or biocompatible barrier forming material.
• In an embodiment, therelease element130 includes a release element configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to an energetic stimulus, also illustrated asstimulus192. In an embodiment, an energetic stimulus may include at least one of a mechanical stimulus, a non-ionizing radiation stimulus, an ionizing radiation stimulus, a chemical stimulus, an acoustic stimulus, an ultrasound stimulus, a radio wave stimulus, a microwave stimulus, a light wave stimulus, or a thermal stimulus.
• In an embodiment, therelease element130 is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to at least one of terahertz radiation, microwave radiation, and radio wave radiation, also illustrated as thestimulus192. For example, radio wave radiation may include, for example, at least one of ultra-high frequency radio waves (UHF), very high frequency radio waves (VHF), radio frequency (RF), or extremely low frequency (ELF) radio waves. In an embodiment, therelease element130 includes at least one of a foil, gold foil, a liposome, wax, dielectric/wax composite. An example of a microwave responsive liposome is described in U.S. Pat. No. 4,801,459 to R. Liburdy. An example of a microwave responsive material, including a wax and a wax/dielectric composite, is described in United States Patent Application Publication No. 2005/0191708 to R. Saul, et al. In an embodiment, the release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a magnetic stimulus. In an embodiment, the release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to an electric field stimulus.
• In an embodiment, the release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a chemical stimulus (not shown). For example, a chemical stimulus may include at least one of a stimulus based on pH change, enzymatic exposure or catalysis. In an embodiment, a chemical stimulus may include a stimulus operable to release or reverse a cooperative or a reversible molecular binding, or a stimulus operable to form an irreversible binding.
• In an embodiment, therelease element130 is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a mechanical agitation stimulus (not shown). For example, a mechanical agitation stimulus may include a shaking or spinning to rupture a membrane or a seal or a foil. In an embodiment, a release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an ex vivo exposure to a mechanical stimulus (not shown). For example, a mechanical stimulus may include shaking a piercing member against a foil release element. In an embodiment, the release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an ex vivo exposure to the stimulus, the release element including a mechanically activatable structure (not shown). For example, the mechanically activatable structure may include a foil or a pressure-rupturable membrane, or a heat-activatable structure.
• In an embodiment, therelease element130 is permeated, dissolved, or disintegrated in response to the stimulus. In an embodiment, a release element is changed such that it is permeated, dissolved, or disintegrated in response to an in vivo environment of theanimal198 where it would not have been so before exposure to the stimulus. In an embodiment, a release element is changed such that it forms a barrier, or is impermeable, solid, or integral in response to the exposure to the stimulus where it would not have been so before the exposure to the stimulus.
• In an embodiment, therelease element130 is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to at least one of a thermal, acoustic stimulus and ultrasound. Examples of an acoustically active release element formed by conjugating liposomes and microbubbles are described in A. Kheirolomoom, et al.,Acoustically-active microbubbles conjugated to liposomes: Characterization of a proposed drug delivery vehicle,118 J CONTROLRELEASE, Issue 3, April 23; 118(3):275-284. Epub 2006 December 23.
• In an embodiment, therelease element 130 includes a release element configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an ex vivo exposure to at least one of an activation stimulus, or an actuation stimulus. In an embodiment, the release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a de-activation stimulus.
• In an embodiment, therelease element130 includes a release element configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to an ultrasound stimulus. For example, the release element may include at least one of liposomes, lipid microspheres, microbubbles, lipospheres, or liposomes responsive to an ultrasound stimulus, which are described in U.S. Pat. No. 6,416,740 to Unger. In an embodiment, the release element includes at least one of polyanhidrides, polyglycolides, polyactides, poly(vinyl acetate), poly(glycolic acid), poly(ethylene), poly(lactic acid), or chitosan. An example of ultrasound-responsive polymer is described in J. Kost, et al.,Ultrasound-enhanced polymer degradation and release of incorporated substances,86 PROCEEDINGS OF THENATIONALACADEMY OFSCIENCES OF THEUSA, 7663-7666 (1989). In this article, Kost describes up to a 5-fold reversible increase in degradation rate and up to 20-fold reversible increase in release rate of incorporated molecules were observed with biodegradable polyanhydrides, polyglycolides, and polylactides. This article also describes up to a 10-fold reversible increase in release rate of incorporated molecules within nonerodible ethylene/vinyl acetate copolymer were also observed. The release rate increased in proportion to the intensity of ultrasound. Temperature and mixing were relatively unimportant in effecting enhanced polymer degradation, whereas cavitation appeared to play a significant role. Another example of ultrasound-responsive polymer is described in J. Kost, et al.,Ultrasonically controlled polymeric drug delivery,Makromolekulare Chemie 19 MACROMOLECULARSYMPOSIA275-285 (1988). In this article, Kost describes investigation of polymers that include lactic acid polymer, glycolic acid polymer, ethylene copolymer, vinyl acetate copolymer. An example of ultrasound-responsive chitosan is described in M. Tsaih, et al.,Effect of the degree of deacetylation of chitosan on the kinetics of ultrasonic degradation of chitosan;90 JOURNAL OFAPPLIEDPOLYMERSCIENCE3526-3531 (2003).
• In an embodiment, therelease element130 includes at least one of polymeric micelle, liposome, lipid microsome, polymeric microsphere, nanoparticle, clathrate compound, cyclodextrin, gel, gel matrix, hydrogel, or cellulose. Examples of polymeric micelles are described in U.S. Pat. No. 7,229,973 to Bae, et al. Bae describes polymeric micelles including mixed micelles containing poly(L-histidine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer. Examples of polymer microspheres are described in U.S. Pat. No. 5,718,921 to Mathiowitz, et al. Mathiowitz describes polymer microspheres built using polyanhydrides, polyorthoesters, polylactic acid polymers, and combinations thereof. Examples of cyclodextrin are described in U.S. Pat. No. 7,270,808 to Cheng, et al., titled “Cyclodextrin-based polymers for therapeutics delivery.” Examples of hydrogels are described in Lin et al.,Hydrogels in controlled release formulations: Network design and mathematical modeling,ADVANCEDDRUGDELIVERYREVIEWS58 (2006) 1379-1408). Examples of cellulose are described in U.S. Pat. No. 6,821,531 to Kumar.
• In an embodiment, therelease element130 includes a release element enclosing thechamber120, configured in a first medicament-release state, and modifiable ex vivo to a second medicament-release state by an exposure to a stimulus, illustrated as thestimulus192. For example,FIG. 1 illustrates an embodiment where theouter layer110 has a spherical shape, the chamber may have similar nested spherical shape, and the release element having a spherical shape and surrounding the chamber. However, nothing in this document expresses or implies a required similarity of shape among one or more of the chamber, the release element, or the outer layer. For example, an embodiment may include a liposome forming the release element and functionally defining a chamber.
• In an embodiment, therelease element130 includes or defines a release element encapsulating the chamber. In an embodiment, the release element includes a release element encapsulating themedicament190 in cooperation with thechamber wall122, configured in a first medicament-release state, and modifiable ex vivo to a second medicament-release state by an exposure to the stimulus. For example,FIG. 2, infra, illustrates arelease element230 encapsulating themedicament190 in cooperation with achamber220 as expressed or defined by achamber wall222. In an embodiment, the release element includes a release element obstructing an aperture of the chamber. For example,FIG. 3, infra, illustrates arelease element330 in cooperation with achamber320 as expressed by achamber wall322 obstructing anaperture332 of the chamber and preventing a discharge of themedicament190 along afluid communication path336 In an embodiment, the release element includes at least two particles each collectively or respectively forming a chamber carrying a respective instance of the medicament. For example,FIG. 4, infra, illustrates arelease element430 that includes aparticle432 forming a chamber carrying an instance of themedicament190. An example of theparticle432 is additionally described in conjunction withFIGS. 16,20, and23, and respective corresponding particle orpolymeric material1180,1580, and1680. The particle is configured in a first medicament-release state, and modifiable ex vivo to a second medicament-release state by an exposure of the at least two particles to the stimulus. For example, the particle may include a clathrate compound forming a host/guest relationship with molecules of a medicament. For example, the particle may include at least one of hydrogels, liposomes, or dendrimers configured to carry the medicament in an association with their pores, interstitial cavities, structural interstices, bonds, or amorphous cavities.
• In an embodiment, the release element includes a labile bond between a molecule of the medicament and a bioactivity inhibiting molecule configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure of the labile bond to the stimulus (not shown).
• Referring again toFIG. 1, in an embodiment, therelease element130 is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to the stimulus, and configured to contain themedicament190 at least until thefinal dosage form102 is administered into theanimal198.
• FIG. 1 illustrates an embodiment having thechamber120 formed within theouter layer110 and configured to carry themedicament190. In an embodiment, thechamber120 is substantially defined within the outer layer and configured to carry the medicament until released by the release element. For example,FIG. 2 illustrates an embodiment that includes thechamber220 substantially defined within theouter layer210 and configured to carry themedicament190 until released by therelease element230.FIG. 3 illustrates an embodiment that includes thechamber320 substantially defined within theouter layer310 and configured to carry themedicament190 until released by therelease element330.
• In an embodiment (not shown), the release element and chamber both may be formed by a particle, such as a liposome, or a hydrogel. In such embodiment, the chamber includes at least one chamber substantially within the outer layer of the particle and configured to carry the medicament.
• In an embodiment, thechamber120 includes a chamber configured to confine themedicament190 in cooperation with therelease element130. In an embodiment (not shown), the chamber includes at least one chamber configured to confine the medicament in a structural cooperation with the release element. In an embodiment (not shown), the chamber is configured to initially carry the medicament. The chamber is also configured to release at least a portion of the medicament upon at least one of a reconfiguration, bursting, puncture, permeation, dissolution, and disintegration of therelease element130.
• In an embodiment (not shown), thechamber120 includes a first chamber configured to carry a first medicament and a second chamber configured to carry a second medicament. An example of the first chamber configured to carry a first medicament and the second chamber configured to carry a second medicament is described in conjunction withFIG. 5 andchamber520A andchamber520B. In an embodiment (not shown), the chamber includes a first chamber configured to carry a first constituent of the medicament and a second chamber configured to carry a second constituent of the medicament. In an embodiment (not shown), the chamber includes a first chamber configured to carry a first reactant of the medicament and a second chamber configured to carry a second reactant of the medicament. In an embodiment (not shown), a combination of the first reactant and the second reactant in response to an ex vivo exposure of the release element initiates a chemical activation or a synthesis of the medicament and a physical releasability of the medicament. In an embodiment (not shown), a combination of the first reactant and the second reactant in response to an ex vivo exposure of the release element initiates a chemical activation or a synthesis of the medicament but does not provide a physical releasability of the medicament. In an embodiment, the resulting medicament product can be released in vivo through the release characteristics of the outer layer. Alternatively, the physical releasability of the medicament may occur by another ex vivo exposure of the dosage form to a stimulus, such as thestimulus192.
• In an embodiment shown inFIG. 1, thefinal dosage form102 includes acontainment element140 retaining themedicament190 within the final dosage form until the dosage form is administered to theanimal198. The containment element can be used in situations where the medicament is a liquid or other material that is prone to seepage or discharge through the outer layer. In embodiment, the containment element may include a separate structure, such as a film or coating, retaining the medicament. Such acontainment element140 may form an exterior layer over theouter layer110, or may form a layer interposed between theouter layer110 and thechamber120. In an embodiment, thecontainment element140 may inhibit a discharge of themedicament190 from thefinal dosage form102 prior to its introduction into theanimal198, without regard to whether the release element is in its first medicament-release state or its second medicament-release state. In an embodiment, thecontainment element140 includes acontainment element140 retaining themedicament190 within thefinal dosage form102 until thefinal dosage form102 is exposed to an in vivo environment in theanimal198, and to modulate a release of at least a portion of themedicament190 in vivo upon administration of thefinal dosage form102 to theanimal198. In an embodiment, the containment element may be formed by a combination of theouter layer110 and therelease element130.
• In an embodiment, thecontainment element140 includes a containment layer configured to encompass themedicament190 within thefinal dosage form102 until the final dosage form is administered to theanimal198. For example, thecontainment element140 may include a coating covering theouter layer110 of thefinal dosage form102, such as an enteric coating configured to prevent a release of the medicament from the final dosage form until the final dosage form is administered to the animal. In another example, thecontainment element140 may include a coating covering therelease element130 of thefinal dosage form102. In an embodiment, the containment element includes a containment envelope retaining the medicament within the final dosage form until the dosage form is administered to the animal.
• In an embodiment, thecontainment element140 includes an enteric coating. The enteric coating may include gelatin or cellulose encapsulation. In an embodiment, the containment element includes a hydroxypropyl methylcellulose acetate succinate (HPMCAS) based coating or a methacrylic acid copolymer based coating, for example such as described in U.S. Pat. No. 7,138,143 to Mukai, et al. In an embodiment, the containment element includes a polymer coating, such as an acidic group-containing (meth)acrylate copolymer, shellac, HPMCP (hydroxypropylmethylcellulose phthalate), CAP (cellulose acetate phthalate), HIPMC-AS (hydroxypropylmethylcellulose acetate succinate) or polyvinyl acetate phthalate, for example such as described in U.S. Pat. No. 6,887,492 to Kay, et al. In an embodiment, the containment element includes a polymer coating of a (meth)acrylate copolymer comprising free-radical polymerized C.sub. 1-to C.sub.4-alkyl esters of acrylic or methacrylic acid and (meth)acrylate monomers with a quatemary anunonium group in the alkyl radical, a (meth)acrylate copolymer of 20 to 40% by weight of polymerized ethyl acrylate and 60 to 80% by weight of polymerized methyl methacrylate, ethylcellulose or polyvinyl acetate. For example, as described in U.S. Pat. No. 6,897,205 to Beckert et al. In an embodiment, the containment element includes a cellulose acetate phthalate polymer coating material, for example, as described in U.S. Pat. No. 5,686,106 to Kelm, et al. In an embodiment, the containment element includes a cellulose acetate phthalate; cellulose acetate trimellitate; hydroxypropyl methylcellulose phthalate; hydroxypropyl methylcellulose acetate succinate; polyvinyl acetate phthalate; poly(methacrylic acid, methyl methacrylate) 1:1; or poly(methacrylic acid, ethyl acrylate) 1:1; and compatible mixtures thereof. In another embodiment, the containment element includes a poly(methacrylic acid, methyl methacrylate) 1:2, or a mixture of poly(methacrylic acid, methyl methacrylate) 1:1 and poly(methacrylic acid, methyl methacrylate) 1:2 in a ratio of about 1:10 to about 1:2. For example, as described in U.S. Pat. No. 5,686,105 to Kelm, et al.
• In an embodiment illustrated inFIG. 2 infra, thecontainment element240 includes acontainment element240 configured to prevent a release of themedicament190 from thefinal dosage form202 until thefinal dosage form202 is introduced into theanimal198.
• Returning toFIG. 1, in an embodiment, themedicament190 includes at least one of an agent, treatment agent, drug, prodrug, therapeutic, nutraceutical, medication, vitamin, nutritional supplement, medicine, remedy, medicinal substance, or cosmetic. In an embodiment, the medicament includes a first reactant of the medicament and a second reactant of the medicament. In an embodiment, the medicament includes at least one prodrug and optionally an activating-enzyme of the prodrug. In an embodiment, the chamber includes a first chamber configured to carry a prodrug, and a second chamber configured to carry an activating enzyme of the prodrug.
• In an embodiment, thefinal dosage form102 may further include aindicator element180 configured to indicate an exposure of therelease element130 to thestimulus192. In an embodiment, theindicator element180 includes anindicator element180 configured to optically indicate an exposure of the release element to thestimulus192 by at least one of dielectric, a conductivity, or ultrasonic profile responsive to an exposure of the release element to the stimulus. Theindicator element180 including, for example, at least one of 4-keto-bacteriorhodopsin films, cinnamylidene acetyl chloride, α-methylcinnamylidene acetyl chloride, α,γ-dimethylcinnamylidene acetyl chloride, α-phenylcinnamylidene acetyl chloride, α-phenoxycinnamylidene acetyl chloride, and cyanocinnamylidene acetyl chloride, leuco dye-serum albumin albumin complexes, azo dyes, or poly(ethylene glycol). Examples of bacteriorhodopsin films are described in A. Druzhko, et al., 4-Keto-bacteriorhodopsin films as a promising photochromic and electrochromic biological material,BIOSYSTEMS. 1995; 35(2-3): 129-32. Examples of hydrophilic photosensitive polymers are described in U.S. Pat. No. 5,990,193 to Russell, et al. Examples of photosensitive compositions for detection of radiation in the ultraviolet wavelength, including leuco dye-serum albumin complexes, are described in U.S. Pat. No. 4,466,941 to Cerami, et al. Examples of using azo dye for an indicator is described in U.S. Pat. No. 5,679,442. Examples of poly(ethylene glycol) are described in U.S. Pat. No. 5,990,193 to Russell, et al., and in Zhong, et al.,Photodegradation Behavior of Polycaprolactone-Poly(ethylene glycol)Block Copolymer,Vol. 10, No. 4 CHINESECHEMICALLETTERS327-330 (1999).
• In an embodiment depicted inFIG. 1, theindicator element180 includes an electronically-detectable indicator element180 configured to indicate an exposure of therelease element130 to thestimulus192. For example, the electronically-detectable indicator element180 may include a substance, material, or device having a conductive property that makes an electronically-detectable change in response to an exposure to thestimulus192. An example of such substance, material, or device includes a shape memory alloy switch that responds to heat described in U.S. Pat. No. 5,410,290 to Cho. Other examples of such substances, materials, or devices include a material that polymerizes in the presence of an ultrasound and changes a conductive property in response, such as the ultrasonic polymerization of methyl methacrylate described in U.S. Pat. No. 5,466,722 to Stoffer, et al., the heat or UV radiation triggered polymerization of acrylamide, or the microwave triggered polymerization of trimethylene carbonate. Another example of such substances, materials, or devices include the use of bistable compounds whose conductivity changes based upon exposure to electromagnetic radiation as described in U.S. Pat. No. 7,175,961 to Beck, et al. Another example includes a metal film or foil degradable by microwaves to release the medication whose state can degradation detected electrically.
• In an embodiment, theindicator element180 includes an electronically-detectable indicator element180 configured to indicate an exposure of therelease element130 to thestimulus192. For example, the electronically-detectable indicator element180 may include a dielectric element having a property that makes an electronically-detectable change in response to an exposure to thestimulus192. An example of such a dielectric element may include a one-time programmable memory cell described in U.S. Pat. No. 7,256,446, to Hu, et al., or a switch comprising microelectromechanical elements described in U.S. Pat. No. 7,336,474 to Lerche, et al.
• In an example, the electronically-detectable indicator element180 may include an element having a permittivity that makes an electronically-detectable change in response to an exposure of the release element to thestimulus192. An example of such an element having a permittivity may include photonic crystals whose permittivity changes through the addition of photonic and/or electrical energy as described in U.S. Pat. No. 6,859,304 to Miller, et al.
• In another example, the electronically-detectable indicator element180 may include an element having an ultrasonic profile that makes an ultrasound-discernable change in response to an exposure of the release element to thestimulus192. An example of an element having an ultrasonic profile that includes a polymer monitorable using the continuous wave ultrasonic process monitor is described in U.S. Pat. No. 7,017,412 to Thomas, et al. Another example of an element having an ultrasonic profile that includes a polymer monitorable using the apparatus for degree on doneness is described in U.S. Pat. No. 7,191,698 to Bond, et al. A further example of an element having an ultrasonic profile that includes a degradable metal film or metal foil.
• In another example, the electronically-detectable indicator element180 may include a carrier, admixture, diluent, or excipient having a property that makes an ultrasound-discernable change in response to an exposure of the release element to thestimulus192. For example, an admixture may include a phase change material (PCM) as an inert filler and having a property that makes an ultrasound-discernable change in response to an exposure of the release element to ultrasound. Examples of such PCMs include polyvinyl alcohol (PVA)-stearic acid (SA) and polyvinyl chloride (PVC)-stearic acid (SA). An example of Polymer-stearic acid blend is described in Ahmet Sari, et al.,Polymer-stearic acid blends as form-stable phase change material for thermal energy storage,64 JOURNAL OF SCIENTIFIC&INDUSTRIAL RESEARCH, at pp. 991-996 (December 2005). Other examples are described in United States Patent Application No. 2007/0249753 to Lin, et al. (polyether fatty-acid ester (polyethylene glycol or polytetramethylene glycol base polymer), and U.S. Pat. No. 5,565,132 to Salyer (Addition of microwave absorber to make PCM materials sensitive to microwaves). Ultrasonic detection or discernment of phase changes in a PCM may be implemented using techniques described by A. W. Aziz, & S. N. Lawandy,Ultrasonic detection of segmental relaxations in thermoplastic polyurethanes,31 JOURNAL OFAPPLIEDPOLYMERSCIENCE1585 (Issue 6, 2003) or S. L. Morton,Ultrasonic cure monitoring of photoresist during pre-exposurebake process,ULTRASONICSSYMPOSIUM,1997. PROCEEDINGS.,1997IEEE Volume 1, at 837-840 (October 1997).
• The indicator element180 (as enumerated inFIG. 1) can be made biocompatible so as to not cause an adverse reaction in the animal. Biocompatibility can be achieved through the use of a biocompatible material or through the use of a minimal amount of material so that any adverse reaction to theindicator element180 is minimized.
• FIG. 2 illustrates anenvironment200 that includes theanimal198, a cross-sectional view of an examplefinal dosage form202 for administering themedicament190 to the animal, and theexample stimulation source194 operable to emit thestimulus192. In an embodiment, the final dosage form includes a dosage form having completed a manufacturing or production process. In an embodiment, the final dosage form includes a product, finished tablet, or capsule ready for distribution to a hospital, pharmacy, or retail store for individualizing to a particular animal, such as theanimal198. In an embodiment, the final dosage form may include a tablet shape, a spherical shape, or an ellipsoidal shape. In an embodiment, the final dosage form may include a structure or a particle carryable or transportable by a liquid or other fluid carrier.
• Thefinal dosage form202 includes anouter layer210, therelease element230, and thechamber220 as expressed or defined by thechamber wall222. The release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a stimulus. For example, the stimulus may include thestimulus192. The chamber includes achamber wall222, is substantially within the outer layer, and is configured to carry themedicament190. In an embodiment, the final dosage form may include anindicator element280. In an embodiment, the final dosage form may include acontainment element240.
• Theenvironment200 illustrates an embodiment where therelease element230 encompasses themedicament190 in cooperation with thechamber220 as expressed or defined by thechamber wall222. Theouter layer210 and therelease element230 are cooperatively retaining themedicament190 if the release-element is in a first medicament-release state and allow an in vivo discharge of at least a portion of the medicament from the chamber if the release-element is in a second medicament release state. In an embodiment, the release element may include at least one of a poly(vinyl alcohol), gel, gel matrix, hydrogel, and azopolymer photo or light modifiable substance as described above. In an embodiment, the release element may include at least one of a polyanhidride, polyglycolide, polyactide, poly(vinyl acetate), poly(glycolic acid), poly (ethylene), poly(lactic acid), chitosan, or an acoustic or ultrasound-modifiable substance as described above. For example, when the first medicament-release state is configured to retard medicament release and the second medicament-release state is configured to allow medicament release in vivo, the release element when configured in the first medicament-release state will retard medicament release from the final dosage form upon administration of the final dosage form into the animal. For example, in a first medicament release state, the release element is impermeable to the environment outside the final dosage form, and impermeable to the medicament in the chamber. Following exposure to an appropriately configured stimulus, the release element achieves a second medicament release state that is, for example, permeable to the medicament. The second medicament release state may include, for example, a state where the release element changes shape or size (e.g., expands, shrinks), dissolves, or dissipates upon exposure to an aqueous environment, gastric juices or a certain pH environment.
• FIG. 3 illustrates anon-limiting environment300 that includes theanimal198, a cross-sectional view of an examplefinal dosage form302 for administering themedicament190 to the animal, and theexample stimulation source194 operable to emit thestimulus192. In an embodiment, the final dosage form includes a dosage form having completed a manufacturing or production process. In an embodiment, the final dosage form includes a product, finished tablet, or capsule ready for distribution to a hospital, pharmacy, or retail store for individualizing to a particular animal, such as theanimal198. In an embodiment, the final dosage form may include a tablet shape, a spherical shape, or an ellipsoidal shape. In an embodiment, the final dosage form may include a structure or a particle carryable or transportable by a liquid or other fluid carrier.
• Thefinal dosage form302 includes anouter layer310, achamber320, and arelease element330. The final dosage form also includes arelease passageway332 configured to provide a medicament communication pathway between the chamber and the environment through anaperture334 in the outer layer. The release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a stimulus. For example, the stimulus may include thestimulus192. The chamber includes achamber wall322, is substantially within the outer layer, and is configured to carry themedicament190. In an embodiment, the final dosage form may include anindicator element380. In an embodiment, the final dosage form may include acontainment element340.
• FIG. 3 illustrates a non-limiting embodiment wherein an embodiment of thefinal dosage form302 includes therelease element330 retaining themedicament190 in cooperation with thechamber320 as expressed by thechamber wall322. Theouter layer310 and the release-element330 are cooperatively retaining themedicament190 if the release-element is in one medicament-release state and allowing an in vivo discharge of at least a portion of the medicament from the chamber if the release-element is in another medicament release state. When the release-element is in a state that releases the medicament, the medicament may discharge or flow along thefluid communication path336 expressed or defined at least in part by therelease passageway332.
• In an embodiment, the release element may include at least one of a poly(vinyl alcohol), gel, gel matrix, hydrogel, and azopolymer photo or light modifiable substance as described above. In an embodiment, the release element may include at least one of a foil, gold foil, wax, or dielectric/wax composite microwave modifiable substance. In an embodiment of this example, the release element may include at least one of a polyanhidride, polyglycolide, polyactide, poly(vinyl acetate), poly(glycolic acid), poly(ethylene), poly(lactic acid), chitosan, or an acoustic or ultrasound-modifiable substance as described above. For example, when the first medicament-release state is configured to retard medicament release and the second medicament-release state is configured to allow medicament release in vivo, the release element when configured in the first medicament-release state will retard medicament release from therelease passageway332 and theaperture334 of the final dosage form upon administration of the final dosage form into the animal.
• FIG. 4 illustrates anenvironment400 that includes theanimal198, a cross-sectional view of an examplefinal dosage form402 for administering themedicament190 to the animal, and theexample stimulation source194 operable to emit thestimulus192. In an embodiment, thefinal dosage form402 includes a dosage form having completed a manufacturing or production process. In an embodiment, thefinal dosage form402 includes a product, finished tablet, or capsule ready for distribution to a hospital, pharmacy, or retail store for individualizing to a particular animal, such as theanimal198. In an embodiment, thefinal dosage form402 may include a tablet shape, a spherical shape, or an ellipsoidal shape. In an embodiment, thefinal dosage form402 may include a structure or a particle carryable or transportable by a liquid or other fluid carrier.
• Thefinal dosage form402 includes anouter layer410, achamber420, and arelease element430. The release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to a stimulus. For example, the stimulus may include thestimulus192. The chamber includes achamber wall422, is substantially within the outer layer, and is configured to carry themedicament190. In an embodiment, thefinal dosage form402 may include anindicator element480. In an embodiment, thefinal dosage form402 may include acontainment element440.
• In an embodiment, thechamber420 includes a chamber substantially within theouter layer410 and configured to carry themedicament190. In an embodiment, the chamber encloses at least two structures within the chamber having respective subchambers configured to carry the medicament. For example, such at least two structures may include at least two pores, molecular structures having interstitial cavities, smaller chambers, molecular structure having interstices, or molecular structure having amorphous cavities. In an embodiment, the chamber may contain at least one of an absorbent, liposome, or hydrogel molecular structure which define respective chambers therein. For example, at least two particles may be located in a cavity, such as thechamber120, and in themselves define a distributed chamber by an aggregation of their pores, interstitial cavities, smaller chambers, interstices of a molecular structure, or amorphous cavities. In another example, at least two microparticles may be throughout a carrier having an outer layer, each microparticle having an effective chamber. In an embodiment, the chamber is located substantially within therelease element430. In an embodiment, the distributed chamber is located substantially within theouter layer410.
• Thefinal dosage form402 may include arelease element430 that is associated with themedicament190 in thechamber420. In an embodiment, therelease element430 may include a carrier, admixture, diluent, or excipient configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an ex vivo exposure to thestimulus192. Particles of such a carrier, admixture, diluent, or excipient may be configured to retain or bind to particles of themedicament190 and reduce its bioavailability if the release-element430 is in a first medicament-release state, and release from or unbind particles of themedicament190 and allow an in vivo discharge of at least a portion of themedicament190 from thechamber420 if the release-element430 is in a second medicament release state.
• In an embodiment, an instance of thefinal dosage form402 may carry at least two particles, small particles, or microparticles that each include a portion that forms arelease element430 modifiable ex vivo by exposure to thestimulus192, and a chamber (not shown). The chambers of the at least two particles, small particles, or microparticles each configured to carry a respective instance of the medicament, and collectively forming a distributed chamber. For example, the at least two particles, small particles, or microparticles may include hydrogels, liposomes, or dendrimers having pores, interstitial cavities, structural interstices, bonds, or amorphous cavities configurable to carry molecules of the medicament. The at least two particles, small particles, or microparticles are configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure of the at least two particles, small particles, or microparticles to the stimulus. For example, photosensitive hydrogel particles may carry the medicament. In an embodiment, microwave sensitive liposomes may carry the medicament. In an embodiment, the release element includes a labile bond between a molecule of the medicament and molecule of a bioactivity inhibiting molecule configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure of the labile bond to the stimulus (not illustrated).
• FIG. 5 illustrates anenvironment500 that includes theanimal198, a cross-sectional view of afinal dosage form502 for transporting a medicament to the animal. The medicament is illustrated as afirst medicament190A andsecond medicament190B. In an embodiment, the final dosage form includes a dosage form having completed a manufacturing or production process. In an embodiment, thefinal dosage form502 includes a product, finished tablet, or capsule ready for distribution to a hospital, pharmacy, or retail store for individualizing to a particular animal, such as theanimal198. In an embodiment, thefinal dosage form502 may include a tablet shape, a spherical shape, or an ellipsoidal shape. In an embodiment, thefinal dosage form502 may include a structure or a particle carryable or transportable by a liquid or other fluid carrier.
• Thefinal dosage form502 includes anouter layer510, and at least two dosage elements. The at least two dosage elements are illustrated as A Portion and B Portion, and by “A” and “B” after certain reference numbers inFIG. 5. The A Portion includes achamber520A, arelease element530A, and amedicament190A. In an embodiment, the A Portion includes acontainment element540A. In an embodiment, the A Portion includes anindicator element580A. The B Portion includes achamber520B, arelease element530B, and amedicament190B. In an embodiment, the B Portion includes acontainment element540B. In an embodiment, the B Portion includes anindicator element580B.
• In an embodiment, the A Portion of thefinal dosage form502 may be substantially similar to thechamber120, therelease element130, thecontainment element140, and theindicator element180 ofFIG. 1. In an embodiment, the A Portion may be substantially similar to thechamber220, therelease element230, thecontainment element240, and theindicator element280 ofFIG. 2. In an embodiment, the A Portion may be substantially similar to thechamber320, therelease element330, thecontainment element340, and theindicator element380 ofFIG. 3. In an embodiment, the A Portion may be substantially similar to thechamber420, therelease element430, thecontainment element440, and theindicator element480 ofFIG. 4. Similarly, the B Portion of thefinal dosage form502 may be substantially similar to that described in conjunction with at least one ofFIG. 1,FIG. 2,FIG. 3, orFIG. 4.
• In an embodiment, thefirst medicament190A and thesecond medicament190B may be substantially similar instances of the same medicament. In an embodiment, thefirst medicament190A and thesecond medicament190B may be substantially similar instances of the same medicament, but in substantially differing dosage amounts. For example, thefirst medicament190A may be, for example, a 50-milligram dose of a medicament and thesecond medicament190B may be, for example, a 100-milligram dose of the same medicament. In an embodiment, thefirst medicament190A and thesecond medicament190B may be substantially similar instances of the same medicament, but in substantially differing dosage characteristics, such as a regular release formulation and a sustained release formulation. In an embodiment, thefirst medicament190A and thesecond medicament190B may be different medicaments.
• In use, the A Portion and the B Portion of thefinal dosage form502 may be individually or collectively exposed ex vivo to a stimulus, illustrated as thestimulus192. For example, thefinal dosage form502 can be configured to provide any of three possible dosage levels of the medicament. For example, where thefirst medicament190A is a 50-milligram dose of a medicament and thesecond medicament190B is a 100-milligram dose of a same medicament, where therelease element530A andrelease element530B are modifiable ex vivo by the same stimulus, such as microwave energy, and where the first medicament-release state is configured to retard medicament release in vivo and the second medicament-release state is configured to allow medicament release in vivo, irradiation of the A Portion with microwave energy will actuate the A Portion and make 50-milligrams of the medicament available upon administration of the final dosage form to theanimal198. Similarly, irradiation of the B Portion with microwave energy will actuate the B Portion and make 100-milligrams of the medicament available upon administration of the final dosage form to the animal. Further, irradiation of both the A Portion and the B Portion with microwave energy will actuate both Portions and make 150-milligrams of the medicament available upon administration of the final dosage form to the animal. In another example, thefirst medicament190A is a 100-milligram dose of a first medicament and thesecond medicament190B is a 100-milligram dose of a second medicament. Selective irradiation of the A Portion or the B Portion will make one or both of the medicaments bioavailable upon administration of the final dosage form to the animal. In a further example, therelease element530A is modifiable ex vivo by a first stimulus and therelease element530B is modifiable ex vivo by the second and different stimulus.
• FIG. 6 illustrates anexample environment600 that includes an article ofmanufacture601. The article of manufacture includes apackage660 containing afinal dosage form602 and providing aninstruction670. The final dosage form includes amedicament190, anouter layer610, arelease element630, and achamber620. The release element is configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to an actuation-stimulus. The chamber lies substantially within the outer layer and is configured to carry the medicament. The instruction includes instruction for preparation of the final dosage form for an efficacious administration to an animal by an exposure of the release element of the final dosage form to the stimulus.
• In an embodiment, thefinal dosage form602 may be substantially similar to thefinal dosage form102 ofFIG. 1. In an embodiment, thefinal dosage form602 may be substantially similar to thefinal dosage form202 ofFIG. 2. In an embodiment, thefinal dosage form602 may be substantially similar to thefinal dosage form302 ofFIG. 3. In an embodiment, thefinal dosage form602 may be substantially similar to thefinal dosage form402 ofFIG. 4. In an embodiment, thefinal dosage form602 may be substantially similar to thefinal dosage form502 ofFIG. 5.
• In an embodiment, theinstruction670 includes at least one of information indicating an actuation-stimulus type, an actuation-stimulus wavelength, an actuation-stimulus intensity, an actuation-stimulus duration, a spatial distribution of the stimulus relative to the final dosage form, a target-value for an exposure indicator, or a combination thereof. For example, the information indicating a spatial distribution of the stimulus relative to the final dosage form may include information corresponding to aiming the stimulus, such as toward a right hand portion, a center portion, or a left hand portion of the final dosage form. In an embodiment, the instruction includes an instruction presented by at least one of a label (not shown) on thepackage660, an insert in the package, illustrated as theinstruction670, or an address to electronically published content (not shown). In an embodiment, the instruction includes instruction for preparation of the final dosage form for an efficacious administration to an animal by a human-initiated exposure of the release element of the final dosage form to the actuation-stimulus.
• In an embodiment, thefinal dosage form602 further includes acontainment element640 retaining the medicament within the final dosage form until the final dosage form is introduced into the animal. In an embodiment, the final dosage form includes anindicator element680 configured to indicate an exposure of the release element to the stimulus. In an embodiment, theinstruction670 includes information indicating an expected value of the indicator element.
• FIG. 7 illustrates an exampleoperational flow700 modulating a medicament-release characteristic of a final dosage form. A start operation occurs in anenvironment705 that includes the final dosage form. The final dosage form includes a medicament, an outer layer, a release element configured in a first medicament-release state and modifiable ex vivo to a second medicament-release state by an exposure to the stimulus, and a chamber substantially within the outer layer and configured to carry the medicament. After the start operation, the operational flow includes anindividualization operation710. The individualization operation includes irradiating the release element of the final dosage form ex vivo with a non ionizing radiation, the non-ionizing radiation selected to transform the release element from the first medicament-release state to the second medicament-release state. For example, the irradiating the release element of the final dosage form ex vivo with the stimulus may occur in a hospital pharmacy, a retail pharmacy, a battlefield hospital, a veterinary facility, or other location dispensing medicaments. In another example, the irradiating a release element of the final dosage form ex vivo with the stimulus may occur in a persons home. The operational flow then proceeds to an end operation. In an alternative embodiment, the final dosage form further includes a containment element retaining the medicament within the final dosage form before introduction of the final dosage form into the animal.
• FIG. 8 illustrates an alternative embodiment of theoperational flow700 ofFIG. 7. Theindividualization operation710 may include at least one additional operation. The at least one additional operation may include at least one of an operation712, an operation714, an operation716, an operation718, or an operation722. The operation712 includes irradiating in response to a human-initiated activation a release element of the final dosage form ex vivo with a non-ionizing radiation. The operation714 includes automatically initiating an ex vivo irradiation with a non-ionizing radiation a release element of the final dosage. The operation716 includes irradiating a first release element of the final dosage form ex vivo with a non-ionizing radiation without irradiating a second release element of the final dosage form with the stimulus. The operation718 includes irradiating a first release element of the final dosage form ex vivo with a non-ionizing radiation without irradiating a second release element of the final dosage form with the non-ionizing radiation. The first release element is associated with a first chamber carrying a first instance of the medicament, and the second release element is associated with a second chamber carrying a second instance of the medicament. The operation722 includes irradiating a first release element of the final dosage form ex vivo with a non-ionizing radiation without irradiating a second release element of the final dosage form with the stimulus. The first release element is associated with a first chamber carrying a first medicament, and the second release element is associated with a second chamber carrying a second medicament.
• FIG. 9 illustrates an exampleoperational flow800 fulfilling a request specifying a dose of a medicament for an individual animal. A start operation occurs in an environment that includes a final dosage form. The final dosage form includes an outer layer, a release element configured in a first medicament-release state and changeable to a second medicament-release state by an exposure to the stimulus, a chamber substantially within the outer layer and configured to carry the medicament, and the medicament. In an alternative embodiment, the final dosage form further includes a containment element retaining the medicament within the final dosage form before introduction of the final dosage form into the animal. After the start operation, the operational flow includes a pickingoperation810. The picking operation includes choosing pursuant to the request an instance of a final dosage form that includes the medicament. Adecision operation830 includes selecting a stimulus configured to change or transform a medicament-release state of a release element of the final dosage form. Acustomization operation850 includes initiating an exposure of the release element of the chosen instance of the final dosage form to the selected stimulus. The operational flow then proceeds to an end operation.
• In use of an embodiment, a person such as a pharmacist working in a pharmacy may receive a prescription specifying a dose of a medicament for a patient. A pharmacy typically may have available several different final dosage forms capable of administering the prescribed medicament dose. For example, the available different dosage forms may include at least one of the embodiments of final dosage forms illustrated inFIGS. 1-5. In a picking operation, the pharmacist chooses pursuant to the request an instance of a final dosage form that includes the medicament. In a decision operation, the pharmacist selects a stimulus effective to change a medicament-release state of a release element of the final dosage form. The pharmacist may select the stimulus after consulting with an instruction presented by at least one of a label on box containing the chosen instance of a final dosage form, a package insert in the box, or an address to electronically published content indicated on the label, or package insert. The pharmacist enters the selected stimulus setting for a stimulus emitter, such as thestimulus source194 ofFIG. 1. In a customization operation, the pharmacist initiates an exposure of the release element of the chosen instance of the final dosage form to the selected stimulus. The pharmacist may confirm exposure of the release element to the stimulus by referring to the indicator element. For example, the indicator element may change color in response to an exposure to the selected stimulus. If the prescription specifies multiple doses of the medicament for the patient, the pharmacist may repeat the above sequence until sufficient doses have customized. Alternatively, and if appropriate for the chosen final dosage forms, multiple instances of the final dosage form may be ex vivo exposed to the selected stimulus at one time.
• FIG. 10 illustrates an alternative embodiment of the exampleoperational flow800 ofFIG. 9. The pickingoperation810 may include at least one additional operation. The at least one additional operation may include anoperation812, or anoperation814. Theoperation812 includes choosing pursuant to at least one of an order or a prescription an instance of a final dosage form that includes the medicament. Theoperation814 includes at least one of physically or manually choosing pursuant to the request an instance of a final dosage form that includes the medicament.
• FIG. 11 illustrates another embodiment of the exampleoperational flow800 ofFIG. 9. Thedecision operation830 may include at least one additional operation. The at least one additional operation may include an operation832, an operation834, or an operation836. The operation832 includes selecting a stimulus having an attribute indicated by at least one of a manufacturer of the final dosage form, an instruction packaged with the dosage form, an electronically published content, and a printed publication as effective to change a medicament-release state of a release element of the final dosage form. For example, electronically published content may include a website maintained by the manufacturer of the final dosage form. In a further example, a printed publication may include a reference book, such asPhysician's Desk Reference.The operation834 includes selecting a stimulus configured by at least one of a type, amount, level, wavelength, spectrum, waveform, spatial distribution, duration, or pulse attribute to change a medicament-release state of a release element of the final dosage form. The operation836 includes selecting a stimulus configured to change a medicament-release state of a release element of the final dosage form and to make the request-specified dose of medicament dose bioavailable by the final dosage form.
• FIG. 12 illustrates an embodiment of theexample operation800 ofFIG. 9. Thecustomization operation850 may include at least one additional operation. The at least one additional operation may include an operation852, anoperation854, or anoperation856. The operation852 includes changing a medicament-release state of the release element of the chosen instance of the final dosage form by initiating an exposure of the release element of the chosen instance of the final dosage form to the selected stimulus. Theoperation854 includes preparing a bioavailable dose of the medicament of the final dosage form in fulfillment of the request by initiating an exposure of the release element of the chosen instance of the final dosage form to the selected stimulus. Theoperation856 includes initiating an exposure of the release element of the chosen instance of the final dosage form to the selected stimulus in fulfillment of the request.
• FIG. 13 illustrates an embodiment of the exampleoperational flow800 ofFIG. 9. Theoperation870 may include at least one additional operation. The at least one additional operation may include an operation872, an operation874, or an operation876. Theoperation870 may include at least one additional operation. The at least one additional operation may include an operation872, an operation874, or an operation876. The operation872 includes optically verifying the exposure of the release element of the chosen instance of the final dosage form to the selected stimulus. For example, optically verifying the exposure may be implemented using human vision, machine vision, or ultrasound techniques. The operation874 includes electronically verifying the exposure of the release element of the chosen instance of the final dosage form to the selected stimulus. For example, electronically verifying the exposure of the release element may be implemented using a dielectric element having a property that makes an electronically discernable change in response to an exposure to the stimulus. The operation876 includes quantifying the exposure of the release element of the chosen instance of the final dosage form to the selected stimulus. The operation876 may include at least one additional operation. The at least one additional operation may include an operation878, or anoperation882. The operation878 includes initiating another exposure of the release element of the chosen instance of the final dosage form to the selected stimulus in response to the quantifying the exposure of the release element of the chosen instance of the final dosage form to the selected stimulus. Theoperation882 includes terminating the exposure of the release element of the chosen instance of the final dosage form to the selected stimulus in response to the quantifying the exposure of the release element of the chosen instance of the final dosage form to the selected stimulus.
• FIG. 14 illustrates an embodiment of the exampleoperational flow800 ofFIG. 9. Theoperational flow800 may include at least one additional operation. The at least one additional operation may include anoperation860, anoperation870, or anoperation890. Theoperation860 includes receiving the request specifying a dose of a medicament for an individual animal. Theoperation860 may include at least one additional operation. The at least one additional operation may include an operation862, or an operation864. The operation862 (not shown) includes receiving the request specifying an efficacious medicament dose for an individual animal. The operation864 (not shown) includes receiving the request specifying the final dosage form that includes the medicament for an individual animal.
• Theoperation870 includes verifying the exposure of the release element of the chosen instance of the final dosage form to the selected stimulus. Theoperation890 includes dispensing the chosen instance of the final dosage form after the exposure of the release element of the chosen instance of the final dosage form to the selected stimulus as described above. Theoperation890 may include at least one additional operation, such as an operation892. The operation892 (not shown) includes dispensing the ex vivo exposed instance of the final dosage form in a package bearing an identifier of the individual animal. For example, the identifier may include a name, or identification number of the animal.
• FIG. 15 illustrates anexample environment1000 that includes theanimal198, a cross-sectional view of an examplefinal dosage form1002 for administering themedicament190 to theanimal198, and theexample stimulus source194 operable to emit astimulus192. In an embodiment, the final dosage form includes a dosage form having completed a manufacturing or production process. In an embodiment, the final dosage form includes a product, finished tablet, or capsule ready for distribution to a hospital, pharmacy, or retail store for individualizing for a particular animal. In an embodiment, the final dosage form includes a tablet shape, a spherical shape, or an ellipsoidal shape. In an embodiment, the final dosage form includes a structure, a particle, or a polymer that is carryable or transportable to the animal by a solid, cream, liquid, or fluid carrier.
• Thefinal dosage form1002 includes anouter layer1010, arelease element1030, and themedicament190. The release element is configured in a medicament-holding state. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to a stimulus, illustrated as thestimulus192. In an embodiment, ex vivo includes outside the body of the animal. In an embodiment, ex vivo includes an environment outside or away from the body of the animal. In an embodiment, ex vivo includes outside a living organism, such as “in vitro.” In an embodiment, ex vivo includes an external or ambient environment.
• In an embodiment, thestimulus192 includes at least one of a non-ionizing radiation, an electromagnetic radiation, a magnetic field, an electric field, an energetic stimulus, or a chemical stimulus. In an embodiment, the stimulus includes at least one of a light radiation, terahertz radiation, microwave radiation, or radio wave radiation. In an embodiment, the stimulus includes at least one of a mechanically activatable structure, heat activatable structure, or pressure activatable structure. In an embodiment, the stimulus includes at least one of a thermal, acoustic, or ultrasound stimulus. In an embodiment, the stimulus includes at least one of an activation stimulus, or an actuation stimulus.
• In an embodiment, therelease element1030 includes a release element configured in a medicament-holding state. In the medicament-holding state, themedicament190 is substantially not bioavailable to theanimal198 if thefinal dosage form1002 is administered to the animal. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to thestimulus192. In the medicament-discharge state, the medicament is substantially bioavailable to the animal if the final dosage form is administered to the animal. In an embodiment, substantially not bioavailable to the animal includes having no substantial therapeutic or adverse effect on the animal. In an embodiment, bioavailable to the animal includes the medicament being physiologically available, absorbable, transportable, usable, or utilizable by the animal. In an embodiment, bioavailable to the animal indicates that a portion of an administered dose of medicament reaches the systemic circulation. In an embodiment, not bioavailable to the animal includes the medicament being physiologically not available, not absorbable, not transportable, not usable, or not utilizable by the animal.
• In an embodiment, therelease element1030 includes a release element configured in a medicament-holding state. In the medicament-holding state, themedicament190 is insubstantially bioavailable if thefinal dosage form1002 is administered to theanimal198. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to thestimulus192. In the medicament-discharge state, the medicament is substantially bioavailable if the final dosage form is administered to the animal. In an embodiment, the release element includes a release element configured in a medicament-holding state. In the medicament-holding state, the medicament is substantially bio-unavailable if the final dosage form is administered to the animal. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to the stimulus wherein the medicament is substantially bioavailable if the final dosage form is administered to the animal. In an embodiment, bio-unavailable includes present but not usable by the animal.
• In an embodiment, the release element includes arelease element1030 configured in a medicament-holding state. In the medicament-holding state, themedicament190 has a substantially insignificant effect on theanimal198 if thefinal dosage form1002 is administered to the animal. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to the stimulus. In the medicament-discharge state, the medicament has a substantially significant effect on the animal if the final dosage form is administered to the animal. In an embodiment, the release element includes a release element configured in a medicament-withholding state, and modifiable ex vivo to a medicament-supplying state by an exposure to the stimulus.
• In an embodiment, therelease element1030 includes a release element configured in a medicament-holding state and field-modifiable ex vivo to a medicament-discharge state by an exposure to thestimulus192. For example, the release element may be field modified at a point of administration of the final dosage form, such as clinic or hospital, at a pharmacy such as when a pharmacist is filling a prescription that includes the final dosage form, or at a residence by a caregiver or by a person for whom the final dosage form is prescribed. In an embodiment, the release element includes a release element configured in a medicament-holding state and modifiable ex vivo post-manufacture to a medicament-discharge state by an exposure to the stimulus. In an embodiment, the release element includes a release element forming an imperforate barrier in a medicament-holding state. The release element is modifiable ex vivo by an exposure to the stimulus to form a perforate barrier in a medicament-discharge state. In an alternative embodiment, the release element is modifiable ex vivo by an exposure to the stimulus to form a perforate barrier in a medicament-discharge state to form at least one discharge pathway.
• In an embodiment, therelease element1030 includes a release element configured in a medicament-holding state. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to thestimulus192, the stimulus including at least one of light or radio waves.
• In an embodiment, thefinal dosage form1002 includes a particle or polymer implemented release element. In an embodiment, a polymer may include an intelligent polymer having a changeable property that in one state admits or discharges at least one molecule of medicament and in another state engages or retains the at least one molecule of medicament. An intelligent polymer includes a polymer structurally responsive to an externally applied energy or stimulus. In an embodiment, “applied energy” includes both positive and negative energy values, i.e. supplying and removing energy. Examples of intelligent polymers are described in U.S. Pat. No. 7,104,517 to Derand, et al. In an embodiment, a particle may include a microsphere, polymeric microsphere, or nanoparticle.
• FIG. 16 illustrates anexample environment1100 that illustrates afinal dosage form1102 having arelease element1130 implemented by a characteristic response of a particle or apolymeric material1180 to a stimulus such as, thestimulus192. An example of the particle or polymeric material is illustrated as a liposome. The final dosage form includes molecules of themedicament190 carried by the particle or a polymeric material, again illustrated with respect to the liposome. Example water-soluble drug molecules190A are illustrated as engaged, retained, or entrapped in an internal aqueous compartment site1120A. Example lipid-soluble drug molecules190B are illustrated as engaged, retained or entrapped in abilayer site1120B. Theexample environment1100 illustrates the release element configured in a medicament-holding state with at least one molecule of the medicament engaged, retained or entrapped. In an embodiment, the release element has, for example by application of a stimulus, such as thestimulus192, been changed into a state (not shown) that admits at least one molecule of the medicament, illustrated as the water-soluble drug molecules190A or the lipid-soluble drug molecules190B. The release element state is changed by withdrawal of the stimulus into a state (shown) that engages, retains or entraps the water-soluble drug molecules190A or the lipid-soluble drug molecules190B. Continuing this example, the release element is modifiable ex vivo to a medicament-discharge state by an exposure to a stimulus, such as thestimulus192, which may be the same stimulus used to switch the release element and load the water-soluble drug molecules190A or the lipid-soluble drug190B into the liposome, or may be anotherstimulus192. In an alternative of this example, a chemical stimulus may be used to load the at least one molecule in the liposome, and another stimulus, such as an electromagnetic wave used to modify the liposome to a medicament-discharge state.
• The characteristic response of the particle or polymeric material to thestimulus192 may include any characteristic response that releases an engaged, retained, or entrappedmedicament190 from the particle or polymeric material. For example, a characteristic response of a particular particle or polymeric material may include a releasing bursting, expanding, cleaving, or degradation of the particular particle or polymeric material in response to a microwave stimulus implements therelease element1130.
• In an embodiment, therelease element1130 is configured in a medicament-holding state. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to thestimulus192. The release element including at least one of a gel, gel matrix, hydrogel fibrin, or a dendrimer. Examples hydrogels are described in Y. Qiu, et al,Enivoronment-sensitive hydrogels for drug delivery,SCIENCEDIRECT(October 2001), citingTriggering in Drug Delivery Systems,53 ADVANCEDDRUGDELIVERYREVIEWS321-339 (Issue 3, December 2001). Examples polymers and dendrimers are described in C. Henry,Drug Delivery,80 CHEMICAL& ENGINEERINGNEWS39-47 (No. 34, Aug. 26, 2002) (The drugs are conjugated to the dendrimers using photocleavable or labile linkers, which can be made to release the drug using light or through acid cleavage). Examples of photo-labile, radio-labile, and enzyme-labile dendrimers are described in U.S. Pat. No. 6,471,968 to Baker, et al.; and in U.S. Pat. No. 7,078,461 to Tomalia, et al. In an embodiment, a particle or polymeric material having a characteristic responsive to an exposure to the stimulus include an intelligent or environmentally sensitive particle or polymeric material.
• In an embodiment, therelease element1130 includes a particle (not specifically shown) configured in a medicament-holding state. The particle is modifiable ex vivo to a medicament-discharge state by an exposure to thestimulus192. Examples of environmentally sensitive particles such as microspheres have been described previously herein. In an embodiment, the release element includes a polymer substance configured in a medicament-holding state. The polymer substance is modifiable ex vivo to a medicament-discharge state by an exposure to the stimulus. Examples of environmentally sensitive polymer substances have been described previously herein.
• Returning toFIG. 15, in an embodiment, therelease element1030 includes a non-shape-memory material configured in a medicament-holding state. The non-shape-memory material is modifiable ex vivo to a medicament-discharge state by an exposure to thestimulus192. In an embodiment, the release element includes a release element disposed at least partially within theouter layer1010 and configured in a medicament-holding state. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to the stimulus. In the medicament-discharge state themedicament190 is substantially available for an in vivo release into theanimal198 if the final dosage form is administered to the animal while the release element is configured in the medicament-discharge state.
• In an embodiment, thefinal dosage form1002 further includes achamber1020 located substantially within theouter layer1010 and carrying themedicament190. In an embodiment, thechamber1020 is substantially similar to thechamber120 described in conjunction withFIG. 1. In an embodiment, the final dosage form further includes theindicator element180 configured to indicate an exposure of therelease element1030 to thestimulus192.
• Another embodiment provides afinal dosage form1002 for administering themedicament190 to theanimal198. This embodiment of the final dosage may be illustrated by reference toFIG. 15 and/or by reference toFIG. 16. With reference to an embodiment illustrated byFIG. 15, thefinal dosage form1002 includes arelease element1030, asite1020 carrying the medicament, the medicament, and acontainment element1040. Therelease element1030 is configured in a medicament-holding state and modifiable ex vivo to a medicament-discharge state by an exposure to thestimulus192. The containment element retains the medicament within the final dosage form until the final dosage form is administered to the animal. In an embodiment, the containment element may be substantially similar to thecontainment element140 described in conjunction withFIG. 1.
• With reference to an embodiment illustrated byFIG. 16, an embodiment of the final dosage form includes thefinal dosage form1102 having arelease element1130 formed by a particle orpolymer1180, a site carrying the medicament190 (depicted as the internal aqueous compartment site1120A or as thebilayer site1120B), the medicament. The release element is configured in a medicament-holding state and modifiable ex vivo to a medicament-discharge state by an exposure to the stimulus.
• In an embodiment, thefinal dosage form1102 includes acontainment element1140. The containment element retains the medicament within the final dosage form until the final dosage form is administered to the animal. In an embodiment, thecontainment element1140 includes a particle or polymeric substance retaining themedicament190 within thefinal dosage form1102 until the final dosage form is administered to the animal198 (not shown). For example, the containment element may include a gel, hydrogel, liposome microsphere, polymeric microsphere, dendrimer, or nanoparticle. In an embodiment, the containment element may be another particle or polymer that engages, retains, or entraps the particle or polymer in a containing manner (not shown). In an embodiment, the containment element may be substantially similar to thecontainment element140 of the final dosage from102 described in conjunction withFIG. 1. In an embodiment, the containment element may be substantially similar to the erodibleouter layer110 of thefinal dosage form102 described in conjunction withFIG. 1. In an embodiment, therelease element1130 and the containment element are at least a substantially same structure, for example a microsphere. In an embodiment, the release element and the containment element are substantially different structures, for example a microsphere containment element containing a dendrimer release element. In an embodiment, the containment element includes a carrier, excipient, diluent, or admixture retaining the medicament within the final dosage form until the final dosage form is administered to the animal.
• In an embodiment, the site1120 carrying themedicament190 includes a chamber carrying the medicament. In an embodiment, the site carrying the medicament includes a region carrying the medicament. In an embodiment, the site carrying the medicament includes a binding site releasably carrying the medicament. In an embodiment, the site carrying the medicament includes therelease element1130 or a particle or polymeric material carrying the medicament. In an embodiment, the site carrying the medicament includes a binding site releasably carrying the medicament.
• In an embodiment, the final dosage form includes anindicator element180 configured to indicate an exposure of the release element to the stimulus. With reference to an embodiment illustrated byFIG. 15, thefinal dosage form1002 includes anindicator element180 configured to indicate an exposure of therelease element1030 to thestimulus192. With reference toFIG. 16, thefinal dosage form1102 includes an indicator element (not shown) configured to indicate an exposure of therelease element1130 to thestimulus192.
• FIG. 17 illustrates anexample environment1200 that includes anarticle1201. The article includes at least one final dosage form for administering a therapeutically effective amount of a medicament to an animal. In an embodiment, the final dosage form includes afinal dosage1202 that is substantially similar to thefinal dosage form1002 described in conjunction withFIG. 15. In an embodiment, the final dosage form includes thefinal dosage form1202 that is substantially similar to thefinal dosage form1102 described in conjunction withFIG. 16 (not shown inFIG. 17). The final dosage form ofFIG. 17 includes anouter layer1210, arelease element1230, asite1220 carrying themedicament190. The release element includes a release element configured in a medicament-holding state. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to thestimulus192. The article also includesinstructions1270 for the exposure of the release element to the stimulus sufficient to modify the release element to the medicament-discharge state. In an embodiment, the instructions include instructions specifying the exposure of the release element to a human-initiated stimulus sufficient to modify the release element to the medicament-discharge state. In an embodiment, the instructions include instructions specifying the exposure of the release element to provide an automatically-initiated stimulus sufficient to modify the release element to the medicament-discharge state.
• FIG. 18 illustrates an exampleoperational flow1300 modifying a medicament availability characteristic of a final dosage form. A start operation occurs in anenvironment1305 that includes the final dosage form. The final dosage form includes an outer layer, a release element, a site carrying the medicament, and the medicament. The release element is configured in a medicament-holding state wherein a medicament is substantially not bioavailable to the animal, such as theanimal198. The release element is modifiable ex vivo to a medicament-discharge state by an exposure to the stimulus wherein the medicament is substantially bioavailable to the animal. In an embodiment, the final dosage form is substantially similar to thefinal dosage form1002 described in conjunction withFIG. 15. In an embodiment, the final dosage form is substantially similar to thefinal dosage form1102 described in conjunction withFIG. 16
• After the start operation, theoperational flow1300 includes an activatingoperation1310. The activating operation includes initiating an exposure of a release element of the final dosage form to a stimulus, such as thestimulus192. The initiated stimulus is selected to transform the release element from a medicament-holding state to a medicament-discharge state. In an embodiment, the initiated stimulus includes an initiated stimulus having a parameter selected to transform the release element from a medicament-holding state to a medicament-discharge state. In an embodiment, the initiated stimulus includes an initiated stimulus having at least one of a stimulation characteristic or a spatial characteristic selected to transform the release element from a medicament-holding state to a medicament-discharge state. In an embodiment, the initiating an exposure of a release element of the final dosage form to a stimulus includes initiating a first exposure of a release element of the final dosage form to a stimulus. The initiated first stimulus is selected to transform the release element from a medicament-holding state to a medicament-discharge state. This embodiment further includes receiving an indication of the first exposure of the release element of the final dosage form to the stimulus, the indication generated in response to an indicator element of the final dosage form configured to indicate an exposure of the release element to the stimulus. This embodiment further includes initiating a second exposure of the release element of the final dosage form to the stimulus. The initiated second exposure stimulus is selected to further transform the release element from the medicament-holding state to the medicament-discharge state.
• In an embodiment, the final dosage form includes a containment element retaining the medicament within the final dosage form until the final dosage form is introduced into the animal. In an embodiment, the final dosage form includes an indicator element configured to indicate an exposure of the release element to the stimulus.
• FIG. 19 illustrates an examplefinal dosage form1400 for administering a medicament to an animal. The final dosage includesmeans1410 for protecting the final dosage form from an ex vivo environment. The final dosage form includesmeans1420 for releasing the medicament, configured in a medicament-holding state, and modifiable ex vivo to a medicament-discharge state by an exposure to a stimulus, such as thestimulus192. The final dosage form includes themedicament1430.
• In an embodiment, the final dosage form includesmeans1440 for carrying the medicament. In an embodiment, themeans1440 for carrying the medicament is positioned substantially within themeans1410 for protecting the final dosage form. In an embodiment, the final dosage form includes means1450 for indicating an exposure of the means for releasing the medicament to the stimulus. In an embodiment, the final dosage form includesmeans1460 for containing the medicament within the final dosage form until the final dosage form is introduced into the animal.
• An embodiment provides a final dosage form for administering a medicament to an animal. In this embodiment, the final dosage form includes at least one particle or polymeric material respectively carrying at least one molecule of the medicament. The particle or polymeric material is configured in a medicament-retention state wherein the medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal. The particle or polymeric material is modifiable ex vivo by an exposure to the stimulus to a medicament-release state wherein the medicament is substantially bioavailable to the animal if the final dosage form is administered to the animal. This embodiment is described, for example, by reference toFIG. 16,FIG. 20, and/orFIG. 21. In an embodiment, the particle or polymeric material may include at least one of the particle or polymeric materials previously described. In an embodiment, the particle or polymeric material includes an intelligent particle or polymeric material. In an embodiment, the particle or polymeric material includes a polymer matrix structure responsive to the exposure to a stimulus. In an embodiment, the particle or polymeric material includes at least one of a microparticle, a gel or a dendrimer based microparticle responsive to the exposure to a stimulus. In an embodiment, the particle or polymeric material includes at least one of a noisome, fibrin, polymeric micelle, microsome, cyclodextrin, polymer-medicament conjugate, or cellulose responsive to the exposure to a stimulus. In an embodiment, the particle or polymeric material includes at least one of a gel, a gel matrix, a natural gel, a synthetic gel, a colloid gel, or a hydrogel structure covalently bonded to the medicament using a photo labile bond and responsive to the exposure to a stimulus. A synthetic gel may include cellulose or polymers. In an embodiment, the particle or polymeric material includes at least one of a dendrimer, dendrimsome, dendromsome, dendron (partial dendrimer), or dendriplex material. In an embodiment, the particle or polymeric material includes at least one of an emulsion, nano-emulsion, or double emulsion. In an embodiment, the particle or polymeric material includes at least one of a lipid, cationic lipid, lipid micelle, liposome, lipospheres, acoustically active lipospheres, acoustically-active microbubbles conjugated to liposomes, lipid-coated microbubbles, cerasomes, magnetic liposomes, metallosomes, or a mimetic. Acoustically-active microbubbles conjugated to liposomes are described in A. Kheirolomoom, et al.,Acoustically-active microbubbles conjugated to liposomes: characterization of a proposed drug delivery vehicle,J. CONTROLRELEASE118(3) (Apr. 23, 2007):275-84; Epub Dec. 23, 2006. A cerasomes may include liposomes with a silicate surface. A mimetic may include an artificial micelle or membrane.
• FIG. 20 illustrates anexample environment1500 that includes afinal dosage form1502 configurable to administer a medicament to theanimal198. The final dosage form includes at least one molecule of themedicament190. The final dosage form also includes at least one of a particle orpolymeric material1580, which is depicted as a gel. The particle or polymeric material has acharacteristic response1530 to thestimulus192 that releases an engaged, retained, or entrapped at least one molecule of themedicament190 from the particle or polymeric material. For example, a characteristic response of a particular particle or polymeric material may include a releasing bursting, expanding, cleaving, or degradation of the particular particle or polymeric material in response to a microwave stimulus.
• The at least one particle orpolymeric material1580 respectively carries the at least one molecule of themedicament190. The particle or polymeric material is configured in a medicament-retention state wherein the medicament is substantially not bioavailable to theanimal198 if the final dosage form is administered to the animal. The particle or polymeric material being modifiable ex vivo by an exposure to thestimulus192 to carry the medicament in a medicament-release state wherein the medicament is substantially bioavailable to the animal if the final dosage form is administered to the animal.
• FIG. 21 illustrates anexample environment1600 depicting retention and release states of particle or polymeric material1680 (depicted as a hydrogel) carrying themedicament190 and responsive to anex vivo stimulus192.FIG. 21A illustrates a medicament-release state where two instances of the medicament, collectively labeled “190 Released,” have been released from the particle or polymeric material in a medicament-release state.FIG. 21B illustrates a medicament-retention state where two instances of the medicament, collectively labeled “190 Retained” are carried by the particle or polymeric material in a medicament-retention state. Application of the stimulus ex vivo to the particle or polymeric material switches it from the medicament-retention state to the medicament-release state. For example, an ex vivo application of the stimulus to the hydrogel switches it from a pore “closed” state1630-C to a pore “open” state1630-O.
• Returning toFIG. 16,FIG. 16 illustrates the particle orpolymeric material1180, which is depicted as a liposome. The particle or polymeric material carries themedicament190. The particle or polymeric material is configured in a medicament-retention state wherein the medicament is substantially not bioavailable to the animal if the final dosage form is administered to theanimal198. The particle or polymeric material is modifiable ex vivo by an exposure to thestimulus192 to carry the medicament in a medicament-release state wherein the medicament is substantially bioavailable to the animal if the final dosage form is administered to the animal.
• Returning toFIG. 20, in an embodiment, themedicament190 includes a pharmacologically-active agent. In an embodiment, the medicament includes at least one of an agent, treatment agent, drug, prodrug, therapeutic, nutraceutical, medication, vitamin, nutritional supplement, medicine, remedy, medicinal substance, or cosmetic.
• In an embodiment, the particle orpolymeric material1580 carrying themedicament190 includes a particle or polymeric material conjugated with the medicament. In an embodiment, the particle or polymeric material carrying the medicament includes a particle or polymeric material containing, intertwined, or bound with the medicament. In an embodiment, the particle or polymeric material carrying the medicament includes a particle or polymeric material entrapping the medicament.
• In an embodiment, the particle orpolymeric material1180 carrying themedicament190 includes a particle or polymeric material carrying themedicament190 and configured in a medicament-withholding state. In the medicament-withholding state the medicament is substantially not bioavailable to theanimal198 if thefinal dosage form1102 is administered to theanimal198. The particle or polymeric material is modifiable ex vivo by an exposure to thestimulus192 to carry the medicament in a medicament-supplying state wherein the medicament is substantially bioavailable to the animal if the final dosage form is administered to the animal. In an embodiment, the particle or polymeric material includes a particle or polymeric material carrying the medicament and configured in a medicament-retention state. In the medicament-retention state the medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal. The particle or polymeric material is modifiable ex vivo upon at least one of a post-manufacture or a field exposure to the stimulus to a medicament-release state. In medicament-release state, the medicament is substantially bioavailable to the animal if the final dosage form is administered to the animal. In an embodiment, the particle or polymeric material includes a particle or polymeric material carrying the medicament and configured in a medicament-holding state. In the medicament-holding state the medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal. The particle or polymer material is modifiable ex vivo to an in vivo release-facilitation state by an exposure to the stimulus to a medicament-release state. In the in vivo release-facilitation state the medicament is substantially bioavailable to the animal if the final dosage form is administered to the animal.
• In an embodiment, the particle orpolymeric material1580 includes a particle or polymeric material having a premodification characteristic that results in an insignificant uptake of the particle or polymeric material in the gastrointestinal tract of theanimal198. In an embodiment, the particle or polymeric material includes an intact particle or polymeric material having a premodification characteristic that results in an insignificant uptake of the particle or polymeric material in the gastrointestinal tract of the animal. In an embodiment, the particle or polymeric material includes at least one of a gel, gel matrix, or hydrogel structure covalently bonded to the medicament using a photo labile bond. An example of a medicament covalently bonded to a hydrogel using photo labile bonds, and the medicament is not be released unless the gel matrix is exposed to enough light to break the bonds is described in U.S. Pat. No. 6,985,770 to Nyhart, Jr. An example of a medicament conjugated to dendrimers using photocleavable or labile linkers, which can be made to release the drug using light or through acid cleavage is described in Y. Qiu, supra., and C. Henry, supra. In an embodiment, the particle or polymeric material includes at least one of a dendrimer, dendrimsome, or dendriplex material. Examples of photo-labile, radio-labile, and enzyme-labile dendrimers are described in U.S. Pat. No. 6,471,968 to Baker, et al.; and examples of photo labile biocompatible dendrimers made from poly(propyleneimine) (POPAM) interiors and poly(amidoamine) (PAMAM) are described in U.S. Pat. No. 7,078,461 to Tomalia, et al.
• In an embodiment, the particle orpolymeric material1580 includes a liposome carrier entrapping the medicament and having an intact particle size resulting in an insignificant uptake in the gastrointestinal tract of theanimal198. In an embodiment, the particle or polymeric material includes a liposome carrier having a particle size of at least approximately three microns. An example of a liposome carrier having a particle size of at least approximately three microns resulting an insignificant uptake in the gastrointestinal tract of the animal is described in D. Deshmukh,Can intact liposomes be absorbed in the gut? LIFESCI.1981 January 19;28(3):239-42; See also, MARCJ. OSTRO, LIPOSOMES: FROMBIOPHYSICS TOTHERAPEUTICS140 (1987); 42 J. PHARMACY ANDPHARMACOLOGY821-826 (1990); 86 INTER.J. PHARMACY239-246 (1992); PHARMACEUTICALPARTICULATECARRIERS: THERAPEUTICAPPLICATIONSCh. 4 (p. 65, andFIGS. 15 and 16 at page 92) (edited By Alain Rolland 1993). In an embodiment, the particle or polymeric material includes a liposome having a particle size of at least approximately four microns.
• In an embodiment, the particle orpolymeric material1580 includes at least one of a nanoparticle, a microsphere, or a polymeric microsphere responsive to the exposure to thestimulus192. In an embodiment, the particle or polymeric material includes a pharmaceutically-acceptable inert particle or polymeric material.
• In an embodiment, thestimulus192 includes a non-ionizing radiation stimulus. In an embodiment, the stimulus includes an electromagnetic radiation stimulus. In an embodiment, the stimulus includes at least one of a light radiation, terahertz radiation, microwave radiation, and radio wave radiation stimulus. In an embodiment, the stimulus includes a magnetic stimulus. In an embodiment, the stimulus includes an electric stimulus. In an embodiment, the stimulus includes an energetic stimulus. In an embodiment, the stimulus includes a chemical stimulus. In an embodiment, the stimulus includes at least one of a mechanical, heat, or pressure stimulus. In an embodiment, the stimulus includes at least one of an activation stimulus, or an actuation stimulus. In an embodiment, the stimulus includes at least one of at least one of a thermal, acoustic, or ultrasound stimulus. In an embodiment, the stimulus includes a stimulus facilitating a release of the medicament by at least one of an expansion of a gel, gel matrix, or hydrogel carrier. In an embodiment, the stimulus includes a stimulus facilitating a release of the medicament by at least one of an expansion of a gel, gel matrix, or hydrogel carrier to allow a diffusion and bioavailability of the medicament. In an embodiment, the stimulus includes a stimulus facilitating the release of the medicament from the particle or polymeric carrier by at least one of a bursting of a liposome material, formation of a pore in a liposome material, or an unpacking of the particle or polymeric material.
• In an embodiment, the particle orpolymeric material1580 includes a particle or polymeric material carrying themedicament190 and configured in a medicament-retention state wherein the medicament is substantially not bioavailable to theanimal198 if the final dosage form is administered to the animal. The particle or polymeric material modifiable ex vivo by an exposure to thestimulus192 to carry the medicament in a medicament-release state allowing an in vivo release of the medicament if the final dosage form is administered to the animal.
• In an embodiment, the particle orpolymeric material1580 includes a first particle or polymeric material carrying themedicament190, and a second particle or polymeric material (not shown) carrying the first particle or polymeric material. The second particle or polymeric material is configured in a first particle or polymeric material-retention state wherein the first particle or polymeric material is substantially not bioavailable to the animal if the final dosage form is administered to theanimal198. The second particle or polymeric material is modifiable ex vivo by an exposure to thestimulus192 to carry the medicament a first particle or polymeric material-release state wherein the first particle or polymeric material is substantially bioavailable to the animal if the final dosage form is administered to the animal.
• In an embodiment, thefinal dosage form1502 further includes atransport medium1560 suitable for administering the particle orpolymeric material1580 carrying the medicament to theanimal198. For example, the transport medium may include a carrier, admixture, diluent, or excipient. In another example, the transport medium may include a polymer, such as a hydrogel. An example of a polymer transport medium is described in United States Patent Application Pub. 2008/0050445 by Alcantar. In an embodiment, the final dosage form further includes an indicator substance (not illustrated) configured to indicate an exposure of the particle or polymeric substance to thestimulus192. In an embodiment, the final dosage form further includes an indicator substance (not illustrated) configured to visually indicate an exposure of the particle or polymeric substance to thestimulus192.
• An embodiment includes the final dosage form for administering themedicament190 to theanimal198. In this embodiment, the final dosage form includes the medicament and a particle or polymeric material. The particle or polymeric material carries the medicament. The particle or polymeric material is configured in a medicament-retention state wherein the medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal. The particle or polymeric material is modifiable ex vivo by an exposure to a first stimulus to carry the medicament a first medicament-release state wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The particle or polymeric material is modifiable ex vivo by an exposure to a second stimulus to carry the medicament in a second medicament-release state wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. Understanding of this embodiment may be facilitated by reference to the preceding description in conjunction withFIG. 16,FIG. 20, orFIG. 21.
• In an embodiment, the first bioavailability includes a first delivery rate of the medicament and the second bioavailability includes a second delivery rate of the medicament. For example, the particle or polymeric material may have a characteristic that include an adjustable pore size responsive to a temperature of the particle or polymeric material attained in response to a heat stimulus. The heat stimulus may include a microwave or a light source. The first stimulus may include an exposure of the particle or polymeric material to a first temperature, or to a given temperature for a first period of time. The second stimulus may include an exposure of the particle or polymeric material to a second temperature, or to a given temperature for a second period of time. For example, selective control of temperature-modulatable materials is described in G. Rao, et al.,Synthesis of Smart Mesoporous Materials,MRS BULLETINP7.8 (Spring 2003). For example, an adjustable porosity of an organic polymer membrane is described in R. Estrada, et al.,Smart polymeric membranes with adjustable pore size,52 International journal of polymeric materials 833-843 (No. 9, 2003). For example, a thermosensitive grafted polymeric system which can be triggered to release the loaded drug with an increase in temperature, induced by a magnetic thermal heating event, is described in I. Ankareddi, et al.,Development of a Magnetically Triggered Drug Delivery System using Thermoresponsive Grafted Polymer Networks with Magnetic Nanoparticles,2 NANOTECH431-434 (Vol. 2, 2007). See also, R. Liburdy, et al.,Microwave-triggered liposomal drug delivery: investigation of a model drug delivery system,Engineering in Medicine and Biology Society 1163-1164, (Vol. 4, November 1989) (Images of the Twenty-First Century, Proceedings of the Annual International Conference of the IEEE Engineering). In another example, the first stimulus may include a first ultrasound power density and the second stimulus may include a second ultrasound power density. For example, bioavailability of polymeric micelles as a variable function of ultrasound power density is at least suggested by A. Marin, et al.,Acoustic activation of drug delivery from polymeric micelles: effect of pulsed ultrasound,71 JOURNAL OFCONTROLLEDRELEASE239-249 (Issue 3, 28 Apr. 2001).
• In an embodiment, thefinal dosage form1502 configurable to administer a medicament to theanimal198 includes acontainment element1540. In an embodiment, thecontainment element1540 may be substantially similar to thecontainment element140 described in conjunction withFIG. 1. In an embodiment, thecontainment element1540 includes a pH-sensitive component of a liposome. For example, S. Cho, et al,pH-dependent release property of dioleoylphosphatidyl ethanolamine liposomes,25 KOREANJOURNAL OFCHEMICALENGINEERING390 (No. 2, 2008) describes a pH-sensitive liposome prepared by a detergent removal method that retains at neutral pH (6-8), and releases at pH 5. In an embodiment, the containment element includes tunable component of a liposome. For example, I. Hafez, et al.,Tunable pH-Sensitive Liposomes Composed of Mixtures of Cationic and Anionic Lipids,79 BIOPHYSICALJOURNAL1438 (Issue 3, 2000) describes a tunable liposome using cationic and anionic lipid mixtures (cholesteryl hemisuccinate (CHEMS) and N,N-dioleoyl-N,N-dimethylammonium chloride. In an embodiment, the containment element includes pH sensitive Chitosan and polyacrylamide copolymer hydrogels releasing contained substances upon pH changes. For example, as described in P. Bonina, et al., 19 JOURNAL OFBIOACTIVE ANDCOMPATIBLEPOLYMERS101 (No. 2, 2004). In an embodiment, the containment element includes a pH sensitive Chitosan and polyalkyleneoxide-maleic acid copolymer releasing substances on pH changes. For example, as described in T. Yoshizawa, et al.,pH-and temperature-sensitive permeation through polyelectrolyte complex films composed of chitosan and polyalkyleneoxide-maleic acid copolymer,241 JOURNAL OFMEMBRANESCIENCE347 (Issue 2, 2004). In an embodiment, the containment element includes an acrylic acid (AA) grafted onto porous polypropylene (PP) producing a pH sensitive membrane. For example, as described in Y. Wang, et al.,pH sensitive polypropylene porous membrane prepared by grafting acrylic acid in supercritical carbon dioxide,45 POLYMER855 (No. 3, 2004).
• FIG. 22 illustrates anexample environment1700 that includes an article ofmanufacture1701. The article of manufacture includes at least onefinal dosage form1702 for administering themedicament190 to theanimal198. The final dosage form includes the medicament, a particle orpolymeric material1780 carrying the medicament, and aninstruction1770. In an embodiment, the particle or polymeric material carrying the medicament may include the particle or polymeric material described in conjunction withFIG. 20. In an embodiment, the particle or polymeric material carrying the medicament may include a particle or polymeric material described in this paper. An embodiment of the particle or polymeric material carrying the medicament is depicted inFIG. 22 as a gel material for illustrative purposes. The particle or polymeric material has acharacteristic response1730 to thestimulus192 that releases an engaged, retained, or entrapped at least one molecule of themedicament190 from the particle or polymeric material. For example, a characteristic response of a particular particle or microparticle may include a releasing bursting, expanding, cleaving, or degradation of the particular particle or microparticle in response to a microwave stimulus.
• The particle orpolymeric material1780 is in a medicament-retention state wherein the medicament is substantially not bioavailable to theanimal198 after administration of the final dosage form. The particle or polymeric material is modifiable ex vivo to a medicament-release state by an exposure to thestimulus192 wherein the medicament is substantially bioavailable to the animal after administration of the final dosage form.
• Theinstruction1770 includes an instruction for the exposure of the particle orpolymeric material1780 to a human-initiatedstimulus192 sufficient to transform the particle or polymeric material to allow a discharge of at least a portion of the therapeutically effective amount of the medicament from the particle or polymeric carrier.
• In an embodiment, the article ofmanufacture1701 further includes a label associated with the at least onefinal dosage form1702 or an insert into apackage1760 containing the at least one final dosage form, the insert providing theinstructions1770. In an embodiment, the final dosage form further includes atransport medium1765 suitable for administering the particle orpolymeric material1780 carrying themedicarnent190 to the animal195. In an embodiment, the final dosage form further includes an indicator substance (not shown) configured to indicate an exposure of the particle or polymeric material to thestimulus192.
• FIG. 23 illustrates anexample environment1800 that includes afinal dosage form1802 for administering themedicament190 to theanimal198. The final dosage form includes at least one molecule of the medicament and a particle orpolymeric carrier1880, is depicted as a gel, and which is operable to bind the at least one molecule of the medicament. The particle or polymeric carrier is configured in a first medicament-bioavailability state, and modifiable ex vivo to a second medicament-bioavailability state by an exposure to a stimulus, illustrated as thestimulus192. In an embodiment, the particle or polymeric carrier operable to bind the at least one molecule of the medicament has acharacteristic response1830 to a stimulus, such as thestimulus192, that releases the bound at least one molecule of themedicament190 from the particle or polymeric carrier. An example of such characteristic response is described in conjunction withFIG. 21. In another embodiment, the particle or polymeric carrier operable to bind the at least one molecule of the medicament has acharacteristic response1830 to a stimulus, such as thestimulus192, that unbinds or releases the at least one molecule of themedicament190 from the particle or polymeric carrier.
• In an embodiment, the particle orpolymeric carrier1880 includes a pharmaceutically-acceptable inert particle or polymeric carrier operable to bind the at least one molecule of themedicament190. In an embodiment, the particle or polymeric carrier includes a particle or polymeric carrier operable to engage, retain, or entrap at least one molecule of the medicament.
• In an embodiment, the first medicament-bioavailability state is configured to retard medicament release in vivo and the second medicament-bioavailability state is configured to allow medicament release in vivo. In an embodiment, the first medicament-bioavailability state is configured to allow medicament release in vivo and the second medicament-bioavailability state is configured to retard medicament release in vivo.
• In an embodiment, the particle orpolymeric carrier1860 includes a liposome carrier operable to bind the at least one molecule of themedicament190 and having an intact particle size resulting in an insignificant uptake in the gastrointestinal tract of theanimal198. In an embodiment, liposome carrier operable to bind the at least one molecule of the medicament and having an intact particle size resulting in an insignificant uptake in the gastrointestinal tract of the animal includes a liposome carrier operable to bind the at least one molecule of the medicament and having an intact particle size of at least approximately one micron. For a description of an example, see, P. Hoet, et al.,Nanoparticles—known and unknown health risks,2 JOURNAL OFNANOBIOTECHNOLOGY12, at section 4 (2004). In an embodiment, the liposome carrier operable to bind the at least one molecule of the medicament and having an intact particle size resulting in an insignificant uptake in the gastrointestinal tract of the animal includes a liposome carrier operable to bind the at least one molecule of the medicament and having an intact particle size of at least approximately three microns. In an embodiment, the liposome carrier operable to bind the at least one molecule of the medicament and having an intact particle size resulting in an insignificant uptake in the gastrointestinal tract of the animal includes a liposome carrier operable to bind the at least one molecule of the medicament and having an intact particle size of at least approximately four microns.
• In an embodiment, thefinal dosage form1802 further includes atransport medium1860 suitable for administering to theanimal198 the particle orpolymeric carrier1880 holding the at least one molecule of themedicament190. In an embodiment, the final dosage form of claim further includes an indicator substance (not shown) configured to visually indicate an exposure of the particle or polymeric carrier holding the at least one molecule of the medicament to thestimulus192.
• In an embodiment, thefinal dosage form1802 configurable to administer amedicament190 to theanimal198 includes acontainment element1840. In an embodiment, thecontainment element1840 may be substantially similar to thecontainment element140 described in conjunction withFIG. 1. In an embodiment, thecontainment element1840 may be substantially similar to thecontainment element1540 described in conjunction withFIG. 20.
• FIG. 24 illustrates anexample environment1900 that includes afinal dosage form1905 and anoperational flow1910. The final dosage form includes the medicament and a particle or polymeric material. The particle or polymeric material carries the medicament in the medicament-retention state wherein the medicament is substantially not bioavailable if the final dosage form is administered to the animal, such as theanimal198. The particle or polymeric material is transformable to the medicament-release state by the exposure to a stimulus, such as thestimulus192, wherein the medicament is substantially bioavailable if the final dosage form is administered to the animal. In an embodiment, the final dosage form is at least similar to thefinal dosage form1102 described in conjunction withFIG. 16. In an embodiment, the final dosage form is at least similar to thefinal dosage form1502 described in conjunction withFIG. 20. In an embodiment, the final dosage form may is least similar to thefinal dosage form1802 described in conjunction withFIG. 23. After a start operation, the operational flow includes anactivation operation1920. The activation operation includes initiating an exposure of the particle or polymeric material of the final dosage form to a stimulus, such as thestimulus192 previously described. The initiated stimulus is selected to transform the particle or polymeric material from the medicament-retention state to the medicament-release state.
• In an embodiment, thefinal dosage form1905 further includes a containment element retaining the medicament within the final dosage form until the final dosage form is introduced into the animal. In an embodiment, the final dosage form further includes an indicator element configured to indicate an exposure of the particle or polymeric material to the stimulus.
• FIG. 25 illustrates alternative embodiments of theactivation operation1920 ofFIG. 24. The activation operation may include anoperation1922, anoperation1924, or anoperation1926. Theoperation1922 includes an initiated stimulus having a parameter selected to transform the particle or polymeric material from a medicament-retention state to a medicament-release state. Theoperation1924 includes an initiated stimulus having at least one of a stimulation characteristic or a spatial characteristic selected to transform the particle or polymeric material from a medicament-retention state to a medicament-release state. Theoperation1926 includes initiating a first exposure of a particle or polymeric material of the final dosage form to a stimulus, the first initiated stimulus selected to transform the particle or polymeric material from a medicament-retention state to a medicament-release state. Theoperation1926 also includes receiving an indication of the first exposure of the release element of the final dosage form to the stimulus, the indication generated in response to an indicator element of the final dosage form configured to indicate an exposure of the release element to the stimulus. Theoperation1926 further includes initiating a second exposure of the release element of the final dosage form to the stimulus, the initiated second exposure stimulus selected to further transform the release element from the medicament-holding state to the medicament-discharge state.
• FIG. 26 illustrates an example embodiment of afinal dosage form2002 for administering a medicament, such as themedicament190 as previously described, to an animal, such as theanimal198 as previously described. The final dosage form includesmeans2010 for entrapping at least one molecule of the medicament. The final dosage form also includes means2020 for controlling an availability of the entrapped at least one molecule of medicament, wherein the entrapped at least one molecule of medicament is initially substantially not bioavailable if the final dosage form is administered to the animal. The availability of the entrapped medicament is modifiable ex vivo by an exposure to a stimulus, such as thestimulus192 described above, to be substantially bioavailable if the final dosage form is administered to the animal. The final dosage form further includesmeans2030 for protecting themeans2010 for entrapping at least one molecule of the medicament from an ex vivo environment of the final dosage form. The final dosage form also includes themedicament190.
• In an embodiment, the means2020 for controlling an availability of the entrapped at least one molecule of medicament includesmeans2022 for controlling an availability of the entrapped at least one molecule of medicament and having a premodification characteristic resulting in an insignificant uptake in the gastrointestinal tract of the animal. In an embodiment, the final dosage form further includes means2050 for indicating an exposure to the stimulus by the means for controlling an availability of the entrapped at least one molecule of medicament. In an embodiment, the final dosage form further includesmeans2060 for containing the medicament within the final dosage form before the final dosage form is administered to the animal. In an embodiment, the final dosage form further includesmeans2070 for carrying the final dosage form into the animal.
• FIG. 27 illustrates anexample system2100. The system includes a finaldosage form holder2110 configured to carry at least one instance of a final dosage form, illustrated as final dosageform holder portions2102A-2102C. The system also includes thestimulus source194 having at least one controllable stimulus parameter or characteristic, operable to generate thestimulus192, and configured to direct the stimulus toward at least a portion of the final dosage form holder. In an embodiment, the stimulus generator is operable to direct the stimulus toward a selectable portion of the final dosage form holder, such as theportion2102A, or a portion of theportion2102A. The system further includes astimulation controller2140 operable to regulate a controllable parameter of the stimulus source. In an embodiment, the stimulation controller is operable to regulate the controllable stimulus parameter by regulating the stimulus source, by regulating a stimulus transmission pathway between the stimulus source and the final dosage form holder, or by regulating which spatial portion of the dosage form receives the stimulus.
• Thesystem2100 also includes astimulation initiation circuit2160 operable to initiate astimulus192 having a selected stimulus parameter or characteristic in response to a received input. In an embodiment, the stimulation initiation circuit is configured to transmit using the user interface2195 a human perceivable indication of an assessed quality or quantity of the stimulus received by a final dosage form. The stimulation initiation circuit may receive input from a human2199, such as pharmacist or health care provider, or from a stimulus assessment circuit2150. The stimulus assessment circuit is operable to monitor the stimulus received by a final dosage form in response to data received from anindicator monitoring circuit2120. The indicator monitoring circuit is operable to monitor an indicator substance portion of the at least one instance of the final dosage form. In an embodiment, the stimulus assessment circuit is operable to generate a signal usable to provide a human perceivable indication of the assessed stimulus received by a final dosage form via the user interface.
• In an embodiment, thesystem2100 includes a final dosageform recognizer circuit2130 operable to generate data usable in distinguishing a final dosage form. In an embodiment, the system includes a release-state selection circuit2165. In an embodiment, the release-state selection circuit is responsive to signals indicative of a chosen medicament bioavailability of a final dosage form. In an embodiment, the release-state selection circuit is responsive to a human2199 initiated input entered into theuser interface2195. In an embodiment, the system includes astimulus selection circuit2170. In an embodiment, the stimulus selection circuit is responsive to data generated by the final dosage form recognizer circuit. In an embodiment, the stimulus selection circuit is responsive to a human2199 initiated input.
• In an embodiment, thesystem2100 includes a computer-readable storage medium2180 configured by a final dosage form andstimulus exposure database2182. The final dosage form and stimulus exposure database may include instructions for modification or state transformation of the final dosage form for an efficacious administration to an animal by an exposure of the final dosage form to a stimulus, such as theinstructions670 ofFIG. 6, theinstructions1270 ofFIG. 17, or theinstructions1770 ofFIG. 22. The final dosage form and stimulus exposure database may include instructions for modification or state transformation of the final dosage form for an efficacious administration to an animal by an exposure of the final dosage form to the stimulus, such as electronically published instructions, or such as indicated by a reference book, such asPhysician's Desk Reference.The final dosage form and stimulus exposure database may include an electronically-stored database relating stimuli and medicament-bioavailability of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-bioavailability of the final dosage form and stimuli.
• In an embodiment, thesystem2100 may be used to modify or transform a bioavailability of a medicament associated with a final dosage form described herein. For example, the system may be used to modify or transform a bioavailability of a medicament associated with thefinal dosage form102 described in conjunction withFIG. 1; thefinal dosage form202 described in conjunction withFIG. 2; with thefinal dosage form302 described in conjunction withFIG. 3; with thefinal dosage form402 described in conjunction withFIG. 4; with thefinal dosage form502 described in conjunction withFIG. 5; with thefinal dosage form602 described in conjunction withFIG. 6; with thefinal dosage form1002 described in conjunction withFIG. 15; with thefinal dosage form1102 described in conjunction withFIG. 16; with thefinal dosage form1202 described in conjunction withFIG. 17; with thefinal dosage form1502 described in conjunction withFIG. 20; with thefinal dosage form1702 described in conjunction withFIG. 22; or with thefinal dosage form1802 described in conjunction withFIG. 23.
• In an embodiment, thesystem2100 may be used to implement an operational flow modifying or transforming a bioavailability of a medicament associated with a final dosage form described herein. For example, the system may be used to implement the exampleoperational flow700 modulating a medicament-release characteristic of a final dosage form described in conjunction withFIG. 7; the exampleoperational flow800 fulfilling a request specifying a dose of a medicament for an individual animal described in conjunction withFIG. 9; the exampleoperational flow1300 modifying a medicament availability characteristic of a final dosage form described in conjunction withFIG. 18; or theexample operation flow1910 described in conjunction withFIG. 24.
• FIG. 28 illustrates anexample environment2200. The environment includes afinal dosage form2210 for administering themedicament190 to theanimal198. The final dosage form includes a particle or polymeric2202 carrying the medicament in a first medicanent-release state wherein the medicament is available to the animal in a first bioavailability if the final dosage form is administered to the animal. The particle or polymeric material is modifiable ex vivo by an exposure to a stimulus, such as thestimulus192 to carry the medicament in a second medicament-release state wherein the medicament is available to the animal in a second bioavailability if the final dosage form is administered to the animal.
• The particle or polymeric material may include a gel, illustrated as ahydrogel2202A, carrying amedicament190A in a first medicament-release state wherein the medicament is available to the animal in a first bioavailability if the final dosage form is administered to the animal. The particle or polymeric material may include a liposome, illustrated as aliposome2202B, carrying amedicament190B in a first medicament-release state wherein the medicament is available to the animal in a first bioavailability if the final dosage form is administered to the animal. The particle or polymeric material may include a nanoparticle, illustrated as ananosphere2202C, carrying amedicament190C in a first medicament-release state wherein the medicament is available to the animal in a first bioavailability if the final dosage form is administered to the animal.
• In an embodiment, the first bioavailability to theanimal198 includes a first bioavailability characteristic to the animal and the second bioavailability to the animal includes a second bioavailability characteristic. In an embodiment, the first bioavailability characteristic includes themedicament190 having a bioavailability in the small intestine of the animal, and the second bioavailability characteristic includes the medicament having a bioavailability in the large intestine of the animal. In an embodiment, the first bioavailability characteristic includes the medicament having a first medicament quantity available to the animal, and the second bioavailability characteristic includes the medicament having a second medicament quantity available to the animal. For example, the first medicament quantity may be 100 mg and the second medicament quantity may be 200 mg. In an embodiment, the first bioavailability characteristic includes the medicament having an immediate release medicament quantity available to the animal, and the second bioavailability characteristic includes the medicament having a time-release medicament quantity available to the animal. In an embodiment, the first bioavailability characteristic includes the medicament having a first time-release rate, and the second bioavailability characteristic includes the medicament having a second time-release rate. In an embodiment, the first bioavailability characteristic includes the medicament having a first release-decay rate medicament release to the animal, and the second bioavailability characteristic includes the medicament having a second release-decay rate medicament release to the animal. In an embodiment, the first bioavailability characteristic includes the medicament having a first pH sensitivity, and the second bioavailability characteristic includes the medicament having a second pH sensitivity.
• In an embodiment, the first bioavailability to theanimal198 includes a first bioavailability characteristic to the animal and the second bioavailability to the animal includes a second bioavailability characteristic. In this embodiment, the second bioavailability characteristic to the animal may include a substantially different bioavailability characteristic to the animal than the first bioavailability characteristic to the animal. In an alternative of this embodiment, the first bioavailability characteristic to the animal includes a first medicament dosage and the second bioavailability characteristic to the animal includes a second medicament dosage. In another alternative of this embodiment, the first bioavailability characteristic to the animal includes a first medicament release kinetic and the second bioavailability characteristic to the animal includes a second medicament release kinetic. In a further alternative of this embodiment, the first bioavailability characteristic to the animal includes a first medicament release profile and the second bioavailability characteristic to the animal includes a second medicament release profile. In an alternative of this embodiment, the first bioavailability characteristic to the animal includes a first medicament release rate and the second bioavailability characteristic to the animal includes a second medicament release rate. In another alternative of this embodiment, the first bioavailability characteristic to the animal includes a first medicament release delay time and the second bioavailability characteristic to the animal includes a second medicament release delay time. In a further alternative of this embodiment, the first bioavailability characteristic to the animal includes a first medicament release pH dependence and the second bioavailability characteristic to the animal includes a second medicament release pH dependence.
• In an embodiment, the particle orpolymeric material2202 carrying themedicament190 includes an inert particle or polymeric material carrying the medicament. In an embodiment, the particle or polymeric material carrying the medicament includes a particle or polymeric material carrying the medicament in an association. In an embodiment, the particle or polymeric material carrying the medicament includes a particle or polymeric material encapsulating the medicament. In an embodiment, the particle or polymeric material carrying the medicament includes a particle or polymeric material encompassing the medicament. In an embodiment, the particle or polymeric material carrying the medicament includes a particle or polymeric material at least one of engaging, retaining, or binding the medicament. In an embodiment, the particle or polymeric material carrying the medicament includes a particle or polymeric material carrier conjugated with the medicament. In an embodiment, the particle or polymeric material carrying the medicament includes the medicament taken-up by the particle or polymeric material.
• In an embodiment, thefinal dosage form2210 further includes atransport medium2280 suitable for delivering the particle or polymeric material binding the medicament to the animal. In an embodiment, the transport medium may include a carrier, admixture, diluent, or excipient. In an embodiment, the final dosage form includes an indicator substance (not illustrated) associated with the particle or polymeric material and configured to indicate an exposure to the stimulus of the particle or polymeric material carrying the medicament.
• FIG. 29 illustrates anexample environment2300. The example environment includes afinal dosage form2310 for administering themedicament190 to theanimal198. The final dosage form includes a dosage portion labeled as “A Portion” carrying amedicament190A in a first medicament-release state wherein the medicament is bioavailable to the animal if the final dosage form is administered to the animal. In an embodiment, the dosage portion “A” includes achamber2320A defining achamber periphery2322A. The final dosage portion includes another dosage portion labeled as “B Portion” carrying anothermedicament190B and including arelease element2330B in a first medicament-release state wherein the another medicament has a first bioavailability to the animal if the final dosage form is administered to the animal in the first medicament-release state. The release element is modifiable ex vivo to second medicament-release state by an exposure to stimulus, wherein the another medicament has a second bioavailability to the animal if the final dosage form is administered to the animal in the second medicament-release state. In an embodiment, the dosage portion “B” includes achamber2320B defining achamber periphery2322B.
• FIG. 30 illustrates anexample environment2400 that includes afinal dosage form2405 and anoperational flow2410. The final dosage form includes a medicament. The final dosage form also includes a particle or polymeric material carrying the medicament in a first medicament-release state wherein the medicament is available to the animal in a first bioavailability if the final dosage form is administered to the animal. The particle or polymeric material is modifiable ex vivo by an exposure to a stimulus to carry the medicament in a second medicament-release state wherein the medicament is available to the animal in a second bioavailability if the final dosage form is administered to the animal. In an embodiment, the final dosage form may be implemented using thefinal dosage form2210 described in conjunction withFIG. 28.
• Theoperational flow2410 includes, after a start operation, amodification operation2420. The modification operation includes transforming the particle or polymeric material to the second medicament-release state by initiating an ex vivo exposure of the particle or polymeric material to the stimulus. The operational flow includes an end operation. In an embodiment, themodification operation2420 may be implemented using thesystem2100 described in conjunction withFIG. 27.
• FIG. 31 illustrates an example article ofmanufacture2502 for administering medicament to an animal. The article includesmeans2510 for releasably encompassing a medicament in a first state wherein the medicament is available to the animal in a first bioavailability if the final dosage form is administered to the animal. The means for releasably encompassing the medicament in a first state is modifiable ex vivo by an exposure to a stimulus to releasably encompass the medicament in a second state, wherein the medicament is available to the animal in a second bioavailability if the final dosage form is administered to the animal. The article also includes themedicament190.
• In an embodiment, thearticle2502 includesmeans2530 for protecting themeans2510 for releasably encompassing the medicament in a first state. In an embodiment, the article includesmeans2550 for indicating an exposure to the stimulus of the means for releasably encompassing the medicament in a first state. In an embodiment, the article includesmeans2560 for containing the medicament within the final dosage form before the final dosage form is administered to the animal. In an embodiment, the article includesmeans2570 for carrying the final dosage form into the animal.
• FIG. 32 illustrates anexample environment2600. The environment includes afinal dosage form2610 for administeringmedicament190 to theanimal198. The final dosage form includes a release-control substance2602 carrying the medicament in a first medicament-release state wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The release-control substance is modifiable ex vivo by an exposure to a first stimulus, such as a first stimulus192A (not separately shown) of thestimulus192, to carry the medicament in a second medicament-release state wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. The release-control substance is modifiable ex vivo by an exposure to second stimulus, such as asecond stimulus190B (not shown) of thestimulus192, to carry the medicament in a third medicament-release state wherein the medicament has a third bioavailability to the animal if the final dosage form is administered to the animal. The final dosage form also includes themedicament190.
• The release-control substance2602 may include a gel, illustrated as ahydrogel2602A carrying amedicament190A in a first medicament-release state wherein the medicament is available to the animal in a first bioavailability if the final dosage form is administered to the animal. The release-control substance may include a liposome, illustrated as aliposome2602B carrying amedicament190B in a first medicament-release state wherein the medicament is available to the animal in a first bioavailability if the final dosage form is administered to the animal. The release-control substance may include a nanoparticle, illustrated as a nanosphere2602C carrying amedicament190C in a first medicament-release state wherein the medicament is available to the animal in a first bioavailability if the final dosage form is administered to the animal.
• In an embodiment, the first bioavailability to theanimal198 includes themedicament190 being substantially not bioavailable to the animal. In an embodiment, the first bioavailability to the animal includes the medicament being substantially bioavailable to the animal. In this embodiment, the second bioavailability to the animal may include the medicament being substantially bioavailable to the animal, wherein the second bioavailability to the animal is substantially different from the first bioavailability to the animal. In an embodiment, the second bioavailability to the animal includes the medicament being substantially not bioavailable to the animal. In an embodiment, the second bioavailability to the animal includes the medicament being substantially bioavailable to the animal. In an embodiment, the third bioavailability to the animal includes the medicament being substantially not bioavailable to the animal. In an embodiment, the third bioavailability to the animal includes the medicament being substantially bioavailable to the animal.
• In an embodiment, the third bioavailability to theanimal198 includes themedicament190 being substantially bioavailable to the animal, wherein the third bioavailability to the animal is substantially different from the second bioavailability to the animal. For example, the third bioavailability may be substantially different from the second bioavailability in dosage amount, dosage rate, or dosage profile. In an embodiment, the third bioavailability to the animal includes the medicament being substantially bioavailable to the animal, wherein the third bioavailability is substantially different from both the first bioavailability and the second bioavailability. In an embodiment, the first bioavailability includes a first bioavailability characteristic, the second bioavailability includes a second bioavailability characteristic, and the third bioavailability includes a third bioavailability characteristic.
• In an embodiment, the release-control substance2602 includes a biocompatible substance. In an embodiment, a biocompatible substance includes a substance having a quality of not having toxic or injurious effects on biological systems of the animal. In another embodiment, a biocompatible substance includes a substance that does not elicit any undesirable local or systemic effects in the animal. In an embodiment, the release-control substance includes a release-control substance having a modifiable medicament release characteristic. In an embodiment, the release-control substance includes a release-control substance carrying themedicament190 in an initial medicament-retention state. In an embodiment, the release-control substance includes a particle. In an embodiment, the release-control substance includes a polymeric material. In an embodiment, the release-control substance includes a small molecule. In an embodiment, the release-control substance includes a capsule structure.
• In an embodiment, the second stimulus192B (not separately shown) includes a substantially different category of stimulus than the first stimulus192A. In an embodiment, the second stimulus has at least a substantially different intensity than the first stimulus. In an embodiment, the second stimulus includes a substantially different duration than the first stimulus. In an embodiment, the second stimulus includes a substantially different waveform than the first stimulus.
• In an embodiment, the release-control substance2602 includes a release-control substance modifiable ex vivo by an exposure of a first portion of the release-control substance to the first stimulus192A to carry the medicament in a second medicament-release state. In this embodiment, the release-control substance includes a release-control substance modifiable ex vivo by an exposure of a second portion of the release-control substance to the second stimulus192B to carry the medicament in a third medicament-release state.
• In an embodiment, thefinal dosage form2610 includes atransport medium2680 configured to facilitate administering the medicament and the release-control substance to the animal. In an embodiment, the final dosage form includes an indicator substance (not shown) configured to indicate an exposure of at least a portion of the release-control substance to at least one of the first stimulus or the second stimulus. In an embodiment, the final dosage form includes an in vivo degradable containment element (not shown) configured to retain the release-control substance until the final dosage form is administered to the animal.
• The following table illustrates several states of an example of the final dosage form2610:

• TABLE 1
  Example bioavailability configurations 1-3

  	Bioavailability of	Bioavailability of	Bioavailability of
  	medicament in a	medicament in a	medicament in a
  Release control	final dosage form	final dosage form	final dosage form
  substancestate	configuration #	1	configuration #2	configuration #3
  First	1	0	0
  medicament-
  release state
  Modified to	0	1	2
  second
  medicament-
  release state
  Modified to	2	2	1
  third
  medicament-
  release state
  0 = the medicament is substantially not bioavailable
  1 = the medicament is substantially bioavailable
  2 = the medicament is substantially bioavailable in a characteristic substantially different that in 1

• FIG. 33 illustrates anexample environment2700 that includes an article ofmanufacture2701. The article of manufacture includes afinal dosage form2710 for administering medicament to theanimal198. The final dosage form includes the medicament190 (not shown). The final dosage form also includes a release-control substance carrying the medicament in a first medicament-release state wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The release-control substance is modifiable ex vivo by an exposure to a first stimulus to carry the medicament in a second medicament-release state wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. The release-control substance is modifiable ex vivo by an exposure to a second stimulus to carry the medicament in a third medicament-release state wherein the medicament has a third bioavailability to the animal if the final dosage form is administered to the animal. In an embodiment, the final dosage form includes atransport medium2780 configured to facilitate administering the medicament and the release-control substance to the animal. In an embodiment, the final dosage form may be substantially similar to thefinal dosage form2610 described in conjunction withFIG. 32. The article of manufacture also includesinstructions2770 specifying an ex vivo exposure of the release-control substance to the first stimulus or to the second stimulus to achieve a selected second medicament release state or a selected third medicament-release state.
• In an embodiment, theinstructions2770 include instructions specifying an ex vivo exposure of the release-control substance to a selected first stimulus or to a selected second stimulus, such that when implemented transform the release-control substance to the selected second medicament-release state or the selected third medicament-release state.
• FIG. 34 illustrates anexample environment2800 that includes afinal dosage form2805 and anoperational flow2810. The final dosage form includes a medicament. The final dosage form also includes a release-control substance carrying the medicament in a first medicament-release state wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The release-control substance is modifiable ex vivo by an exposure to a first stimulus to carry the medicament in a second medicament-release state wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. The release-control substance is modifiable ex vivo by an exposure to second stimulus to carry the medicament in a third medicament-release state wherein the medicament has a third bioavailability to the animal if the final dosage form is administered to the animal. In an embodiment, thefinal dosage form2805 is substantially similar to thefinal dosage form2610 described in conjunction withFIG. 32.
• After a start operation, the operational flow includes anindividualization operation2820. The individualization operation includes transforming the medicament release state of the release-control substance of thefinal dosage form2805 to the second medicament-release state or the third medicament-release state by initiating an ex vivo exposure of the release-control substance respectively to the first stimulus or the second stimulus. The operational flow includes an end operation. In an embodiment, theoperational flow2810 may be implemented using thesystem2100 described in conjunction withFIG. 27.
• FIG. 35 illustrates an alternative embodiment of theindividualization operation2820 ofFIG. 34. The individualization operation may include at least one additional operation. The at least one additional operation includes anoperation2822, or anoperation2824. Theoperation2822 includes modifying the medicament release state of the release-control substance to the second medicament-release state or the third medicament-release state by initiating an ex vivo exposure of the release-control substance respectively to the first stimulus or the second stimulus. In an embodiment, the operational2282 may be implemented using thesystem2100 described in conjunction withFIG. 27. Theoperation2824 includes transforming the medicament release state of the release-control substance to the second medicament-release state or the third medicament-release state by initiating an ex vivo exposure of the release-control substance to a stimulus selected respectively from the first stimulus or the second stimulus. In an embodiment, theoperation2822 may be implemented using thestimulus selection circuit2165 described in conjunction withFIG. 21.
• FIG. 36 illustrates an alternative embodiment of theindividualization operation2820 ofFIG. 34. The individualization operation may include at least one additional operation. The at least one additional operation includes anoperation2832, an operation2834, or anoperation2836. Theoperation2832 includes initiating an ex vivo exposure of the release-control substance respectively to a modification stimulus selected from the first stimulus or the second stimulus. The selected modification stimulus having a parameter operative to transform the release-control substance carrying the medicament from the first medicament-release state to the second medicament-release state or to the third medicament-release state. The operation2834 includes initiating an ex vivo exposure of the release-control substance to a modification stimulus selected from the first stimulus or the second stimulus, the selected modification stimulus operative to transform the release-control substance carrying the medicament from the first medicament-release state to the second medicament-release state or from the first medicament-release state to the third medicament-release state. Theoperation2836 includes initiating an ex vivo exposure of the release-control substance respectively to a stimulus selected from the first stimulus or the second stimulus, the selected stimulus having at least one of a stimulation characteristic or a spatial characteristic operable to transform the release-control substance carrying the medicament from the first medicament-release state to the second medicament-release state or to the third medicament-release state. For example, a stimulation characteristic may include a waveform, duration, or intensity. A spatial characteristic may include initiating an ex vivo exposure of a portion of the release-control substance to the stimulus.
• Theoperations2832,2834, or2286 may be implemented using thestimulus selection circuit2170 described in conjunction withFIG. 21. In another embodiment, the operation3972 may be implemented using a combination of thestimulus selection circuit2170, thecomputing device2175, and/or the final dosage form andstimulus exposure database2182 described in conjunction withFIG. 21.
• FIG. 37 illustrates an alternative embodiment of theoperational flow2810 ofFIG. 34. Theoperational flow2810 may include at least one additional operation, such as achoosing operation2850. The choosing operation includes selecting a medicament-release state from the second medicament-release state and the third medicament-release state in response to a chosen medicament bioavailability of the final dosage form. The choosing operation may be implemented using the release-state selection circuit2165 described in conjunction withFIG. 27. In an embodiment, thestimulus selection circuit2170, thecomputing device2175, and/or the final dosage form and stimulus exposure database2182 (saved on the computer-readable storage medium2180) may cooperatively implement the choosing operation. The choosing operation may include at least one additional operation, such as an operation2860. The operation2860 includes selecting a modification stimulus from the first stimulus and the second stimulus in response to the selected medicament-release state. The operation2860 may be implemented using thestimulus selection circuit2170 described in conjunction withFIG. 27. In an embodiment, the stimulus selection circuit, thecomputing device2175, and/or the final dosage form andstimulus exposure database2182 may cooperatively implement the operation2860.
• FIG. 38 illustrates anexample environment2900 that includes afinal dosage form2905 and anoperational flow2910. The final dosage form includes a medicament. The final dosage form also includes a release-control substance carrying the medicament in a medicament-retention state wherein the medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal. The release-control substance is modifiable ex vivo by an exposure to a first stimulus to carry the medicament in a first medicament-release state wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The release-control substance is modifiable ex vivo by an exposure to a second stimulus to carry the medicament in a second medicament-release state wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. In an embodiment, thefinal dosage form2905 may be substantially similar to thefinal dosage form2610 described in conjunction withFIG. 32.
• After a start operation, the operational flow includes a releasestate choosing operation2920. The release state choosing operation includes automatically selecting a medicament-release state from the first medicament-release state and the second medicament-release state based on a specified medicament bioavailability of the final dosage form. In an embodiment, the specified medicament bioavailable may be indicated by a physician's prescription, a request by a person to receive the final dosage form, or a table. In an embodiment, the release state choosing operation may be implemented using thesystem2100 described in conjunction withFIG. 27. For example, theperson2199 may enter a prescription of 500 mg of penicillin into theuser interface2195. In response thereto, the release-state selection circuit2165 of the system automatically selects a medicament-release state to achieve 500 mg of penicillin from the first medicament-release state and the second medicament-release state based on the specified medicament bioavailability of the final dosage form. In an embodiment, the selection may be facilitated using thecomputing device2175 and information provided by the final dosage form, andstimulus exposure database2182 described in conjunction withFIG. 27.
• Astimulus choosing operation2930 includes automatically selecting a stimulus from the first stimulus and the second stimulus in response to the selected medicament-release state. In an embodiment, the stimulus choosing operation may be implemented using thesystem2100 described in conjunction withFIG. 27. For example, thestimulus selection circuit2170 may implement the stimulus choosing operation. In an embodiment, the stimulus choosing operation may be implemented in part, in whole by, or in cooperation with thecomputing device2175, and/or the final dosage form andstimulus exposure database2182. Adosage configuration operation2940 includes transforming the medicament release state of the release-control substance by initiating an ex vivo exposure of the release-control substance to the selected stimulus. In an embodiment, the dosage configuration operation may be implemented using thesystem2100 described in conjunction withFIG. 27. For example, thestimulus initiation circuit2160 may initiate the ex vivo exposure of the release-control substance to the selectedstimulus192 generated by thestimulus source194. The operational flow includes an end operation.
• FIG. 39 illustrates anexample vehicle3002 for administering a medicament to theanimal198. The vehicle including means3010 for releasably encompassing the medicament in a first medicament-release state wherein the medicament has a first bioavailability to the animal if the vehicle is administered to the animal. The means for releasably encompassing the medicament in a first medicament-release state is modifiable to a second medicament-release state upon an ex vivo exposure to a first stimulus, the medicament in the second medicament-release state having a second bioavailability to the animal if the vehicle is administered to the animal. The means for releasably encompassing the medicament in a first medicament-release state is modifiable to a third medicament-release state upon an ex vivo exposure to a second stimulus, the medicament in the third medicament-release state having a third bioavailability to the animal if the vehicle is administered to the animal. The vehicle also includes themedicament190.
• In an embodiment, the vehicle includesmeans3030 for protecting the means for releasably encompassing the medicament against an ex vivo environment. In an embodiment, the vehicle includesmeans3050 for indicating an exposure of the means for releasably encompassing the medicament to the first stimulus or the second stimulus. In an embodiment, the vehicle includesmeans3060 for containing the medicament within the vehicle before the final dosage form is administered to the animal. In an embodiment, the vehicle includesmeans3070 for carrying the vehicle into the animal.
• Returning toFIG. 27,FIG. 27 illustrates another example ofsystem2100. The system includes the computer-readable storage medium2180 configured to indicate a stimulus to modify ex vivo a bioavailability of a medicament carried by a final dosage form based upon a selected medicament bioavailability of the final dosage form. The system also include aholder2110 configured to establish ex vivo of the animal a location of a final dosage form to receive the indicatedstimulus192 from astimulus source194. The system further includes the stimulus source operable to provide the indicated stimulus. The system also includes astimulation controller2140 operable to regulate an ex vivo exposure of a final dosage form to the indicated stimulus.
• In an embodiment, the computer-readable storage medium2180 includes a computer-readable storage medium configured to indicate a stimulus to modify ex vivo a bioavailability of a medicament carried by a final dosage form based upon a selected medicament bioavailability of the final dosage form. The indicated stimulus includes at least one of a type, time, intensity, wave form, or pulse form characteristic of the stimulus. In an embodiment, the computer-readable storage medium includes a computer-readable storage medium configured to indicate a stimulus to modify ex vivo a bioavailability of a medicament carried by a final dosage form based upon a selected medicament bioavailability of the final dosage form. The computer-readable storage medium is also configured to indicate another stimulus to modify ex vivo a bioavailability of another medicament carried by another final dosage form based upon another selected medicament bioavailability of the another final dosage form. In an embodiment, the computer-readable storage medium includes a computer-readable storage medium configured to indicate a stimulus to modify ex vivo a bioavailability of a medicament carried by a final dosage form based upon a selected medicament bioavailability of the final dosage form. The computer-readable storage mediums is also configured to indicate another stimulus to modify ex vivo a bioavailability of the medicament carried by a final dosage form based upon the selected medicament bioavailability of the final dosage form. In an embodiment, the computer-readable storage medium includes a computer-readable storage medium configured to indicate a stimulus to that is at least one of sufficient, effective, or operable modify ex vivo a bioavailability of a medicament carried by a final dosage form based upon a selected medicament bioavailability of the final dosage form.
• In an embodiment, the computer-readable storage medium2180 includes a computer-readable storage medium configured to indicate astimulus192 operable to modify ex vivo a bioavailability of a medicament carried by a final dosage form based upon a selected medicament bioavailability of the final dosage form. In an embodiment, the computer-readable storage medium includes a computer-readable storage medium configured to indicate a stimulus to substantially modify ex vivo a bioavailability of a medicament carried by a final dosage form based upon a selected medicament bioavailability of the final dosage form. In an embodiment, the computer-readable storage medium includes a computer-readable storage medium configured to indicate a stimulus to modify ex vivo a bioavailability of a medicament carried by a final dosage form based upon a selected treatment using the final dosage form. In an embodiment, the computer-readable storage medium includes a computer-readable storage medium configured to indicate a stimulus to modify ex vivo a bioavailability of a medicament carried by a final dosage form based upon a selected efficacious treatment using the final dosage form.
• In an embodiment, theholder2110 includes a holder operable to locate a final dosage form in a position to receive the indicatedstimulus192 from astimulus source194 before an administration of the final dosage form to theanimal192. In an embodiment, the holder includes a holder operable to establish a location of a final dosage form to receive the indicated stimulus from a stimulus source and ex vivo of the animal. In an embodiment, the holder includes a holder operable to establish ex vivo of the animal a location of at least two instance of a final dosage form to receive the indicated stimulus from a stimulus source.
• In an embodiment, thestimulus source194 includes a stimulus device, circuit, module, or generator operable to provide the indicatedstimulus192 for a final dosage form. In an embodiment, the stimulus source includes a stimulus source operable to produce the indicated stimulus. In an embodiment, the stimulus source includes a stimulus source operable to generate the indicated stimulus. In an embodiment, the stimulus source includes a stimulus source operable to provide the indicated stimulus to at least two instances of the final dosage form. In an embodiment, the stimulus source includes a stimulus source operable to provide the indicated stimulus. The indicated stimulus includes at least one of a mechanical stimulus, a non-ionizing radiation stimulus, an ionizing radiation stimulus, a chemical stimulus, an acoustic stimulus, an ultrasound stimulus, a radio wave stimulus, a microwave stimulus, a light wave stimulus, or a thermal stimulus. In an embodiment, the stimulus source includes a stimulus source operable to provide an indicated stimulus having at least one controllable characteristic. In an embodiment, the stimulus source includes a stimulus source operable to provide the indicated stimulus and to direct the provided stimulus at a portion of the location of a final dosage form established by the holder. In an alternative of the this embodiment, the stimulus source is operable to provide the indicated stimulus and to direct the provided stimulus at a selectable portion of the location of a final dosage form established by the holder. In an embodiment, the stimulus source includes a stimulus source operable to provide the indicated stimulus for a final dosage form and for another final dosage form. In an embodiment, the stimulus source includes a stimulus source operable to provide the indicated stimulus for at least two instances of a final dosage form.
• In an embodiment, thestimulation controller2140 includes a stimulation controller operable to regulate thestimulus source194 in response to a received human-initiated activation input. In an embodiment, the stimulation controller includes a stimulation controller operable to regulate the stimulus source in response to a received feedback device-initiated activation input. In an embodiment, the stimulation controller includes a stimulation controller operable to regulate the stimulus source in response to a received stimulus-selector initiated activation input. In an embodiment, the stimulation controller includes a stimulation controller operable to regulate the stimulus source in response to a received activation input indicating a selected stimulus. In an embodiment, the stimulation controller includes a stimulation controller operable to regulate the stimulus source in response to the indicated stimulus for a final dosage form and in response to a received activation input. In an embodiment, the stimulation controller includes a stimulation controller device, circuit, module, or programmed device operable to regulate an ex vivo exposure of a final dosage form to the indicated stimulus. In an embodiment, the stimulation controller includes a stimulation controller operable to regulate a stimulus transmission pathway between the stimulus source and the holder in response to the indicated stimulus for a final dosage form. In an embodiment, the stimulation controller includes a stimulation controller operable to regulate the stimulus source and direct the stimulus toward a selected portion of a final dosage form carried by theholder2110 in response to the indicated stimulus for the final dosage form, and in response to a received activation input.
• In an embodiment, thestimulation controller2140 includes a stimulation controller operable to regulate a duration of the stimulus, a wave characteristic of the stimulus, an intensity of the stimulus, a density of the stimulus, or amplitude of the stimulus source in response to the indicated stimulus for a final dosage form. In an embodiment, the wave characteristic may include a pulse form or a dynamic waveform.
• In an embodiment, thesystem2100 further includes a stimulus assessment circuit2150 operable to monitor an aspect of the indicatedstimulus192 provided by thestimulus source194. In an embodiment, the stimulus assessment circuit includes a stimulus assessment circuit operable to monitor an aspect of the indicated stimulus received by a final dosage form. In an embodiment, the stimulus assessment circuit includes a stimulus assessment circuit operable to monitor at least one of a type, quantity, or a characteristic of the indicated stimulus received by a final dosage form. In an embodiment, the stimulus assessment circuit includes a stimulus assessment circuit operable to monitor an aspect of the indicated stimulus received by at least a portion of a final dosage form. In an embodiment, the stimulus assessment circuit includes a stimulus assessment circuit operable to monitor an aspect of an indicator substance portion of a final dosage form. In an embodiment, the stimulus assessment circuit includes a stimulus assessment circuit operable to sense a parameter of a final dosage form responsive to the indicated stimulus received by the final dosage form. In an embodiment, the stimulus assessment circuit includes a stimulus assessment circuit operable to monitor an aspect of the indicated stimulus received by a final dosage form, and to generate an output indicative of the monitored aspect of the indicated stimulus received by the final dosage form. In this embodiment, thestimulation controller2140 includes a stimulation controller operable to regulate an ex vivo exposure of a final dosage form to the indicated stimulus in response to the generated output indicative of the monitored aspect of the indicated stimulus received by the final dosage form. In an alternative embodiment, the stimulus assessment circuit includes a stimulus assessment circuit operable to monitor an aspect of the indicated stimulus received by a final dosage form, and to generate an output signal indicative of the monitored aspect of the indicated stimulus received by the final dosage form and receivable by thestimulation controller2140. In an embodiment, the stimulus assessment circuit includes a stimulus assessment circuit operable to generate a signal usable in providing a human perceivable indication of an aspect of the indicated stimulus received by a final dosage form.
• In an embodiment, thesystem2100 further includes anindicator monitoring circuit2120 operable to generate a signal indicative of a status of an indicator substance associated with a final dosage form and configured to indicate an exposure to the indicated stimulus by the final dosage form. In an embodiment, the indicator monitoring circuit includes an indicator monitoring circuit operable to generate signal indicative of at least one of an exposed, exposed to an extent, or not exposed status of an indicator substance associated with a final dosage form and configured to indicate an exposure to the indicated stimulus by the final dosage form. In an embodiment, the indicator monitoring circuit includes an indicator monitoring circuit operable to generate a human perceivable indication of a status of an indicator substance associated with a final dosage form and configured to indicate an exposure to the indicated stimulus by the final dosage form. In an embodiment, the indicator monitoring circuit includes an indicator monitoring circuit operable to generate a machine readable signal indicative of a status of an indicator substance associated with a final dosage form and configured to indicate an exposure to the indicated stimulus by the final dosage form.
• In an embodiment, thesystem2100 further includes astimulus initiation circuit2160 operable to initiate the provision of the indicated stimulus by the stimulation source. In an embodiment, the stimulus initiation circuit includes a stimulus initiation circuit operable to initiate the provision of the indicated stimulus by the stimulation source in response to at least one of a received user input or an automatically generated instruction. In an embodiment, the stimulus initiation circuit includes a stimulus selection circuit operable to select the indicated stimulus for provision by the stimulus source. In an embodiment, the stimulus initiation circuit includes a stimulus selection circuit operable to select the indicated stimulus for provision by the stimulus source in response to at least one of a received user input or in response to an automatically generated input.
• In an embodiment, thesystem2100 further includes a final dosageform recognizer circuit2130 operable to generate data indicative of an identifying characteristic of a final dosage form. The data indicative of an identifying characteristic of the final dosage form may be acquired in response to discernable aspect of the final dosage form, such as a bar code, shape, color, or marking.
• FIG. 40 illustrates an example system3100. The system includes means3110 for persistently storing computer-readable information indicative of a stimulus operable to modify ex vivo a bioavailability of a medicament carried by a final dosage form for administration of the medicament to an animal. The system also includesmeans3120 for establishing ex vivo of the animal a location of the final dosage form to receive the indicated stimulus from a stimulus source. The system further includesmeans3130 for providing the indicated stimulus. The system also includesmeans3140 for regulating an ex vivo exposure of the final dosage form to the indicated stimulus.
• In an embodiment, the means3110 for persistently storing computer-readable information includesmeans3112 for persistently storing computer-readable information indicative of a stimulus to modify ex vivo a bioavailability of a medicament carried by a final dosage form for administration of the medicament to an animal. The computer-readable information indicative of a stimulus based upon a selected medicament bioavailability of the final dosage form.
• FIG. 41 illustrates anexample environment3200. The environment includes afinal dosage form3202 for administering medicament to theanimal198. The final dosage form includes a dosage portion, illustrated as an “A” Portion. The dosage portion has achamber3220A carrying amedicament190A. The dosage portion includes arelease element3230A in a first medicament-release state. In the first medicament state, the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal in the first medicament-release state. The release element is modifiable ex vivo to a second medicament-release state by an exposure to a stimulus192A (not illustrated). In the second medicament-release state, the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal in the second medicament-release state. The final dosage form includes another dosage portion, illustrated as a “B” Portion. The another dosage portion has anotherchamber3220B carrying anothermedicament190B. The another dosage portion includes anotherrelease element3230B in another first medicament-release state. In the another first medicament-release state, the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal in the another first medicament-release state. The another release element is modifiable ex vivo to another second medicament-release state by an exposure to another stimulus192B (not illustrated). In the another second medicament-release state, the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal in the another second medicament-release state. The final dosage form includes anouter layer3210 enclosing the dosage portion and the another dosage portion.
• In an embodiment, the first medicament-release state includes a first medicament-release state wherein themedicament190A is not bioavailable to theanimal198. In an embodiment, the first medicament-release state includes a first medicament-release state wherein the medicament is bioavailable to the animal. In an embodiment, the second medicament-release state includes a second medicament-release state wherein the medicament is not bioavailable to the animal. In an embodiment, the second medicament-release state includes a second medicament-release state wherein the medicament is bioavailable to the animal.
• In an embodiment, the another first medicament-release state includes another first medicament-release state wherein the anothermedicament190B is not bioavailable to theanimal198. In an embodiment, the another first medicament-release state includes another first medicament-release state wherein the another medicament is bioavailable to the animal. In an embodiment, the another second medicament-release state includes another second medicament-release state wherein the another medicament is not bioavailable to the animal. In an embodiment, the another second medicament-release state includes another second medicament-release state wherein the another medicament is bioavailable to the animal.
• In an embodiment of thefinal dosage form3202, if the first medicament-release state includes themedicament190A being bioavailable to the animal and if the another first medicament-release state includes the anothermedicament190B being bioavailable to theanimal198, a first ratio exists between the bioavailability of the medicament and the bioavailability of the another medicament. In this embodiment of the final dosage form, if the second medicament-release state includes themedicament190A being bioavailable to the animal and if the another second medicament-release state includes the anothermedicament190B being bioavailable to the animal, a second ratio exists between the bioavailability of the medicament and the bioavailability of the another medicament. In an embodiment, the first ratio is equal to or greater than the second ratio. In an embodiment, the first ratio is less than the second ratio.
• In an embodiment of thefinal dosage form3202, if the second medicament-release state includes themedicament190A being bioavailable to theanimal198 and if the another second medicament-release state includes the anothermedicament190B being bioavailable to the animal, a second ratio exists between the bioavailability of the medicament and the bioavailability of the another medicament.
• In an embodiment, themedicament190A and the anothermedicament190B are at least substantially similar instances of one medicament. In an embodiment, the medicament and the another medicament are at least substantially different medicaments. In an embodiment, the first bioavailability to the animal includes a first bioavailability characteristic and the second bioavailability to the animal includes a second bioavailability characteristic.
• In an embodiment, therelease element3230A is at least substantially similar to the anotherrelease element3230B. In an embodiment, the release element is at least substantially different from the another release element.
• In an embodiment, thestimulus190A is at least substantially similar to the anotherstimulus190B. In an embodiment, the stimulus is at least substantially different from the another stimulus.
• In an embodiment, thefinal dosage form3202 further includes anindicator element3280A configured to indicate an exposure of therelease element3230A to the stimulus192A or the another stimulus192B. In an embodiment, thefinal dosage form3202 further includes anotherindicator element3280B configured to indicate an exposure of the another release element to the stimulus or the another stimulus. In an embodiment, the final dosage form further includes an indicator element, for example,indicator element3280A, configured to indicate an exposure of at least one of the release element or the another release element to the stimulus or the another stimulus.
• In an embodiment, thefinal dosage form3202 includes acontainment element3240A or acontainment element3240B configured to respectfully retain themedicament190A or the anothermedicament190B until the final dosage form is administered to theanimal198.
• In an embodiment, thefinal dosage form3202 further includes a further dosage portion (not illustrated). The further dosage portion includes a further chamber carrying a further medicament. The further dosage portion also includes a further release element in a further first medicament-release state. In the further first medicament-release state, the further medicament has a further first bioavailability to theanimal198 if the final dosage form is administered to the animal in the further first medicament-release state. The further release element is modifiable ex vivo to a further second medicament-release state by an exposure to a further stimulus. In the further second medicament-release state, the further medicament has a further second bioavailability to the animal if the final dosage form is administered to the animal in the further second medicament-release state.
• The following table illustrates several states of an example of the final dosage form3202:

• TABLE 2
  Example bioavailability configurations

  	Example	Example
  	Configuration #
  1	Configuration #2
  	Bioavailability	Bioavailability
  	Profile	Profile

  		RE 2	RE 1
  	RE 1	(200 mg	(100 mg	RE 2
  State of release element (RE)	(100 mg)	TR)	TR)	(200 mg)
  State 1	0	0	1	0
  (initial)
  State 2	1	0	0	0
  (stimulus to RE of chamber 1)
  State 3	0	1	1	1
  (stimulus to RE of chamber 2)
  State 4	1	1	0	1
  (stimuli to REs ofchambers 1
  & 2)
  0 = medicament is substantially not bioavailable
  1 = medicament is bioavailable

• FIG. 42 illustrates anexample environment3300. The environment includes afinal dosage form3302 for administering medicament to theanimal198. The final dosage form includes a dosage portion, illustrated as “A” Portion, having achamber3320A carrying amedicament190A. The dosage portion includes arelease element3330A in a medicament-retention state. The medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal in the first medicament-retention state. The release element is modifiable ex vivo to a medicament-release state by an exposure to a stimulus. The medicament is bioavailable to the animal if the final dosage form is administered to the animal in the medicament-release state. The final dosage form includes another dosage portion, illustrated as “B” Portion, having anotherchamber3320B carrying anothermedicament190B. The another dosage portion includes anotherrelease element3330B in another medicament-retention state. The another medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal in the another medicament-retention state. The another release element is modifiable ex vivo to another medicament-release state by an exposure to another stimulus. The another medicament is bioavailable to the animal if the final dosage form is administered to the animal in the another medicament-release state.
• FIG. 43 illustrates anexample environment3400 that includes afinal dosage form3405 and anoperational flow3410. The final dosage form includes a dosage portion having a chamber carrying a medicament. The dosage portion also includes a release element in a first medicament-release state. The medicament has a first bioavailability to the animal if the final dosage form is administered to the animal in the first medicament-release state. The release element modifiable ex vivo to a second medicament-release state by an exposure to a stimulus, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal in the second medicament-release state. The final dosage form also includes another dosage portion having another chamber carrying another medicament. The another dosage portion also includes another release element in another first medicament-release state. The another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal in the another first medicament-release state. The another release element modifiable ex vivo to another second medicament-release state by an exposure to another stimulus. The another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal in the another second medicament-release state. In an embodiment, thefinal dosage form3405 may be substantially similar to thefinal dosage form3202 described in conjunction withFIG. 41.
• After a start operation, theoperational flow3410 includes amodification operation3420. The modification operation includes transforming thefinal dosage form3405 into a selected medicament-release profile by initiating an ex vivo exposure of the release element or the another release element to a modification stimulus respectfully selected from the stimulus and the another stimulus. For example, the selected medicament-release profile may include a configuration of bioavailabilities of the medicament and the another medicament to achieve a prescribed medicament dosage. The operational flow includes an end operation. In an embodiment, the operational flow may be implemented using thesystem2100 described in conjunction withFIG. 27.
• FIG. 44 illustrates an alternative embodiment of theoperational flow3410 ofFIG. 43. The operational flow may include at least one additional operation. The at least one additional operation may include a treatment-order operation3450, a release-state selection operation3460, or astimulus selection operation3470. The treatment-order operation includes receiving a signal indicative of a chosen medicament bioavailability of thefinal dosage form3405. In an embodiment, the treatment-order operation may include a medicament bioavailability indicated by a physician's prescription, a request by a person to receive the final dosage form, or a table. In an embodiment, the treatment-order operation may be implemented using thesystem2100 described in conjunction withFIG. 21. The treatment-order operation may include at least one additional operation. The at least one additional operation may include anoperation3452 or anoperation3454. Theoperation3452 includes receiving a machine-initiated signal indicative of the chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation3452 may be implemented using the other circuit(s)2190 to receive data or an email indicative of the chosen medicament bioavailability of the final dosage form. Theoperation3454 includes receiving a signal responsive to human-initiated indication of the chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation3454 may be implemented using theuser interface2195 to receive a human-initiated input by theperson2199.
• The release-state selection operation3460 includes selecting a medicament-release state of the release element or of the another release element in response to the chosen medicament-bioavailability of the final dosage form. In an embodiment, the release-state selection operation may be implemented using thesystem2100 described in conjunction withFIG. 21. The release-state selection operation may include at least one additional operation, such as an operation3462. The operation3462 includes electronically selecting a medicament-release state of the release element or of the another release element in response to the selected medicament-bioavailability of the final dosage form. The selecting a medicament-release state is based on an electronically-stored database relating medicament-release state and medicament-bioavailability of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state and medicament-bioavailability of the final dosage form. In an embodiment, the operation3462 may be implemented using the release-state selection circuit2165 described in conjunction withFIG. 21. In another embodiment, the operation3462 may be implemented using a combination of the release-state selection circuit2165, thecomputing device2175, and/or the final dosage form andstimulus exposure database2182 described in conjunction withFIG. 21.
• Thestimulus selection operation3470 includes selecting the modification stimulus from the stimulus or the another stimulus in response to the selected medicament-release state. In an embodiment, the stimulus selection operation may be implemented using thesystem2100 described in conjunction withFIG. 21. The stimulus selection operation may include at least one additional operation, such as an operation3472. The operation3472 includes electronically selecting the modification stimulus from the stimulus or the another stimulus in response to the selected medicament-release state, the selecting the stimulus based on an electronically-stored database relating stimuli and medicament-release state of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state of the final dosage form and stimuli. In an embodiment, the operation3472 may be implemented using thestimulus selection circuit2170 described in conjunction withFIG. 21. In another embodiment, the operation3472 may be implemented using a combination of thestimulus selection circuit2170, thecomputing device2175, and/or the final dosage form andstimulus exposure database2182 described in conjunction withFIG. 21. Themodification operation3420 is described in conjunction withFIG. 43.
• FIG. 45 illustrates anexample environment3500. The environment includes an article ofmanufacture3501. The article of manufacture includes afinal dosage form502 for administering medicament to an animal. The final dosage form is described in conjunction withFIG. 5. In another embodiment, thefinal dosage form502 is substantially similar to thefinal dosage3310 described in conjunction withFIG. 42.
• The article ofmanufacture3501 also includesinstructions3570 specifying an ex vivo exposure of therelease element530A to the stimulus192A (not shown) of thestimulus192, or an ex vivo exposure of the anotherrelease element530B to the another stimulus192B (not shown) of thestimulus190. The instructions when implemented transform the release element to the second medicament-release state or the another release element to the another second medicament-release state. In an embodiment, the instructions may be implemented using thesystem2100 described in conjunction withFIG. 27.
• FIG. 46 illustrates an example article ofmanufacture3602 for administering medicament to an animal. The article of manufacture includes afirst portion3610 and asecond portion3650. The first portion includesmeans3620 for carrying amedicament190A. In an embodiment, themeans3620 includes means for releasably holding a medicament. The first portion also includes means3624 for medicament release control in a first state wherein the medicament has a first bioavailability to the animal if the article of manufacture is administered to the animal. The means for medicament release control is modifiable ex vivo to a second state by an exposure to a stimulus, wherein the medicament has a second bioavailability to the animal if the article of manufacture is administered to the animal. The first portion further includes themedicament190A. In an embodiment, the first portion includes means3628 for indicating an exposure of the means for medicament release control to the stimulus.
• Thesecond portion3650 includes another means3660 for carrying anothermedicament190B. The second portion also includes another means3664 for medicament release control in another first state wherein the another medicament has another first bioavailability to the animal if the article of manufacture is administered to the animal. The another means for medicament release control is modifiable ex vivo to another second state by an exposure to another stimulus, wherein the another medicament has another second bioavailability to the animal if the article of manufacture is administered to the animal. The second portion further includes the another medicament. In an embodiment, the second portion includes another means3668 for indicating an exposure of the another means for medicament release control to the another stimulus.
• FIG. 47 illustrates anenvironment3700. The environment includes afinal dosage form3702 for administering medicament to theanimal198. The final dosage form includes a dosage portion, illustrated as “A Dosage Portion.” The dosage portion includes amedicament190A. The dosage portion also include arelease element3730A in a first medicament-release state wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal in the first medicament-release state. The release element is modifiable ex vivo to a second medicament-release state by an exposure to a stimulus, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal in the second medicament-release state.
• Thefinal dosage form3702 also includes another dosage portion, illustrated as “Another Dosage Portion.” The another dosage portion includes amedicament190B. The another dosage portion also includes anotherrelease element3730B in another first medicament-release state wherein the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal in the another first medicament-release state. The another release element is modifiable ex vivo to another second medicament-release state by an exposure to another stimulus, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal in the another second medicament-release state.
• In an embodiment, the first medicament-release state wherein the medicament has a first bioavailability to the animal includes a first medicament-release state wherein the medicament is not bioavailable to the animal. In an embodiment, the first medicament-release state wherein the medicament has a first bioavailability to the animal includes a first medicament-release state wherein the medicament is bioavailable to the animal. In an embodiment, the second medicament-release state wherein the medicament has a second bioavailability to the animal includes a second medicament-release state wherein the medicament is not bioavailable to the animal. In an embodiment, the second medicament-release state wherein the medicament has a second bioavailability to the animal includes a second medicament-release state wherein the medicament is bioavailable to the animal. In an embodiment, the first bioavailability to the animal includes a first bioavailability characteristic and the second bioavailability to the animal includes a second bioavailability characteristic.
• In an embodiment, the another first medicament-release state wherein the another medicament has another first bioavailability to the animal includes another first medicament-release state wherein the another medicament is not bioavailable to the animal. In an embodiment, the another first medicament-release state wherein the another medicament has another first bioavailability to the animal includes another first medicament-release state wherein the another medicament is bioavailable to the animal. In an embodiment, the another second medicament-release state wherein the another medicament has another second bioavailability to the animal includes another second medicament-release state wherein the another medicament is not bioavailable to the animal. In an embodiment, the another second medicament-release state wherein the another medicament has another second bioavailability to the animal includes another second medicament-release state wherein the another medicament is bioavailable to the animal.
• In an embodiment, the stimulus includes at least one of a mechanical stimulus, a non-ionizing radiation stimulus, an ionizing radiation stimulus, a chemical stimulus, an acoustic stimulus, an ultrasound stimulus, a radio wave stimulus, a microwave stimulus, a light wave stimulus, or a thermal stimulus.
• FIG. 47 also illustrates another embodiment of theexample environment3700. The environment includes afinal dosage form3702 for administering a medicament to the animal. The final dosage form includes a dosage portion, illustrated as “A” Dosage Portion. The dosage portion includes amedicament190A. The dosage portion also include arelease element3730A. The release element is in a medicament-holding state wherein the medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal in the medicament-holding state. The release element is modifiable ex vivo to a medicament-discharging state by an exposure to a stimulus wherein the medicament is bioavailable to the animal if the final dosage form is administered to the animal in the medicament-discharging state.
• Thefinal dosage form3702 also includes another dosage portion, illustrated as “B” Dosage Portion. The another dosage portion includes amedicament190B. The another dosage portion also includes anotherrelease element3730B in another medicament-holding state wherein the another medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal in the another medicament-holding state. The another release element is modifiable ex vivo to another medicament-discharge state by an exposure to another stimulus wherein the another medicament is bioavailable to the animal if the final dosage form is administered to the animal in the another medicament-discharge state. In an embodiment, thefinal dosage form3702 further includes anouter layer3710 carrying the dosage portion and the another dosage portion.
• The following table illustrates several states of example embodiments of the final dosage form2610:

• TABLE 3
  Example bioavailability configurations

  	Example	Example Configuration #2
  	Configuration #1	Bioavailability Profile

  State of

  Bioavailability Profile

  RE

  1

  RE 2

  release	RE	1	RE 2	(100 mg	(200 mg
  element (RE)	(100 mg)	(200 mg TR)	Medicament A)	medicament B)
  State 1	0	0	0	0
  (initial)
  State 2	1	0	1	0
  (stimulus to
  first RE)
  State 3	0	1	0	1
  (stimulus to
  second RE)
  State 4	1	1	1	1
  (stimuli to
  both REs)
  0 = medicament is substantially not bioavailable
  1 = medicament is bioavailable

• FIG. 48 illustrates anexample environment3800. The example environment includes afinal dosage form3810 for administering medicament to an animal. The final dosage form includes adosage portion3804A, and is illustrated in an embodiment as including two molecules. In another embodiment, the dosage portion may include a large number of molecules. A molecule of the dosage portion includes a release element; the molecule is generally illustrated as including arelease element3802 having a medicament (not shown). In an embodiment, a small molecule includes the release element. In an embodiment, a particle or polymer material includes the release element. In an embodiment, an intelligent molecule includes the release element. In an embodiment, a gel, illustrated as ahydrogel3802A, includes the release element having an associatedmedicament190A. In an embodiment, a liposome, illustrated as aliposome3802B, includes the release element having an associatedmedicament190B. In an embodiment, a nanoparticle includes the release element, illustrated as ananosphere3802C having an associatedmedicament190C.
• Therelease element3802 is in a first medicament-release state wherein the medicament has a first bioavailability to theanimal198 if the final dosage form is administered to the animal in the first medicament-release state. The release element is modifiable ex vivo to a second medicament-release state by an exposure to a stimulus, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal in the second medicament-release state.
• The final dosage form also includes another dosage portion, illustrated as adosage portion3804B, illustrated in an embodiment as including two molecules. In another embodiment, the another dosage portion may include a large number of molecules. A molecule of the another dosage portion includes another release element, generally also illustrated asrelease element3802 having another medicament (not shown). In an embodiment, another small molecule includes the another release element. In an embodiment, another particle or polymer material includes the another release element. In an embodiment, another intelligent molecule includes the another release element. In an embodiment, another gel, illustrated as thehydrogel3802A, includes the another release element having an associatedmedicament190A. In an embodiment, another liposome, illustrated as theliposome3802B, includes the another release element having an associatedmedicament190B. In an embodiment, another nanoparticle, illustrated as thenanosphere3802C, includes the another release element having an associatedmedicament190C.
• The another release element is in another first medicament-release state wherein the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal in the another first medicament-release state. The another release element is modifiable ex vivo to another second medicament-release state by an exposure to another stimulus, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal in the another second medicament-release state.
• WhileFIG. 48 illustrates the molecules comprising releaseelements dosage portion3804A in a proximity, in an embodiment, the molecules comprising releaseelements dosage portion3804A may be distributed in any manner throughout thefinal dosage form3810. Likewise, in an embodiment, the molecules comprising releaseelements dosage portion3804B may be distributed in any manner throughout thefinal dosage form3810. Further, the molecules comprising releaseelements dosage portion3804A and the molecules comprising releaseelements dosage portion3804B may be intermingled in any manner throughout thefinal dosage form3810. In an embodiment, the molecules that comprise thedosage portion3804A and3804B may be substantially a same type of molecule, or may be substantially different types of molecules.
• FIG. 48 also illustrates another embodiment of theexample environment3800. The another embodiment of the example environment includes afinal dosage form3810 for administering medicament to an animal. The final dosage form includes adosage portion3804A, illustrated in an embodiment as including two molecules. A molecule of the dosage portion includes a release element, generally illustrated asrelease element3802, having a medicament (not shown). In an embodiment, a small molecule includes the release element. In an embodiment, a particle or polymer material includes the release element. In an embodiment, an intelligent molecule includes the release element. In an embodiment, a gel, illustrated as ahydrogel3802A, includes the release element having amedicament190A. In an embodiment, a liposome, illustrated as aliposome3802B, includes the release element having amedicament190B. In an embodiment, a nanoparticle includes the release element, illustrated as ananosphere2202C having amedicament190C.
• Therelease element3802 is in a medicament-holding state wherein the medicament is substantially not bioavailable to theanimal198 if thefinal dosage form3810 is administered to the animal in the medicament-holding state. The release element is modifiable ex vivo to a medicament-discharging state by an exposure to a stimulus wherein the medicament is bioavailable to the animal if the final dosage form is administered to the animal in the medicament-discharging state.
• The final dosage form also includes anotherdosage portion3804B, illustrated in an embodiment, as including two molecules. A molecule of the another dosage portion includes another release element, generally also illustrated asrelease element3802 having another medicament (not shown). In an embodiment, another small molecule includes the another release element. In an embodiment, another particle or polymer material includes the another release element. In an embodiment, another intelligent molecule includes the another release element. In an embodiment, another gel, illustrated as thehydrogel3802A, includes the another release element having amedicament190A. In an embodiment, another liposome, illustrated as theliposome3802B, includes the another release element having amedicament190B. In an embodiment, another nanoparticle, illustrated as thenanosphere3802C, includes the another release element having amedicament190C.
• The another release element is in another medicament-holding state wherein the another medicament is substantially not bioavailable to theanimal198 if thefinal dosage form3810 is administered to the animal in the another medicament-holding state. The another release element is modifiable ex vivo to another medicament-discharge state by an exposure to another stimulus wherein the another medicament is bioavailable to the animal if the final dosage form is administered to the animal in the another medicament-discharge state.
• FIG. 49 illustrates anexample environment3900 that includes afinal dosage form3905 and anoperational flow3910. The final dosage form includes a dosage portion having a medicament. The dosage portion includes a release element in a first medicament-release state wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal in the first medicament-release state. The release element is modifiable ex vivo to a second medicament-release state by an exposure to a stimulus, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal in the second medicament-release state. The final dosage form also includes another dosage portion having another medicament. The another dosage portion includes another release element in another first medicament-release state wherein the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal in the another first medicament-release state. The another release element is modifiable ex vivo to another second medicament-release state by an exposure to another stimulus, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal in the another second medicament-release state. In an embodiment, thefinal dosage form3905 is substantially similar to thefinal dosage form3702 described in conjunction withFIG. 47, or thefinal dosage form3810 described in conjunction withFIG. 48.
• After a start operation, theoperational flow3910 includes acustomization operation3920. The customization operation includes transforming thefinal dosage form3905 into a selected medicament release profile by initiating an ex vivo exposure of the release element or the another release element to a modification stimulus respectfully selected from the stimulus or the another stimulus. The operational flow includes an end operation. In an embodiment, the customization operation may include at least one additional operation, such as the operation3922. The operation3922 includes transforming the final dosage form into a selected medicament release profile by initiating an ex vivo exposure of the release element and the another release element to the stimulus and the another stimulus. In an embodiment, theoperational flow3910 may be implemented using thesystem2100 described in conjunction withFIG. 27.
• FIG. 50 illustrates an example alternative embodiment of theoperational flow3910 ofFIG. 49. The operational flow may include at least one additional operation. The at least one additional operation may include a treatment-order operation3950, a release-state selection operation3960, or astimulus selection operation3970. The treatment-order operation includes receiving a signal indicative of a chosen medicament bioavailability of thefinal dosage form3905. In an embodiment, the treatment-order operation may be implemented using thesystem2100 described in conjunction withFIG. 21. The treatment-order operation may include at least one additional operation. The at least one additional operation may include anoperation3952 or anoperation3954. Theoperation3952 includes receiving a machine-initiated signal indicative of the chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation3952 may be implemented using the other circuit(s)2190 to receive data or an email indicative of the chosen medicament bioavailability of the final dosage form. Theoperation3954 includes receiving a signal responsive to human-initiated indication of the chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation3954 may be implemented using theuser interface2195 to receive a human-initiated input by theperson2199 described in conjunction withFIG. 27.
• The release-state selection operation3960 includes selecting a medicament-release state of the release element or of the another release element in response to the chosen medicament-bioavailability of the final dosage form. In an embodiment, the release-state selection operation may be implemented using thesystem2100 described in conjunction withFIG. 21. The release-state selection operation may include at least one additional operation, such as an operation3962. The operation3962 includes electronically selecting a medicament-release state of the release element or of the another release element in response to the selected medicament-bioavailability of the final dosage form. The selecting a medicament-release state is based on an electronically-stored database relating medicament-release state and medicament-bioavailability of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state and medicament-bioavailability of the final dosage form. In an embodiment, the operation3962 may be implemented using the release-state selection circuit2165 described in conjunction withFIG. 21. In another embodiment, the operation3962 may be implemented using a combination of the release-state selection circuit2165, thecomputing device2175, and/or the final dosage form andstimulus exposure database2182 described in conjunction withFIG. 21.
• Thestimulus selection operation3970 includes selecting the modification stimulus from the stimulus or the another stimulus in response to the selected medicament-release state. In an embodiment, the stimulus selection operation may be implemented using thesystem2100 described in conjunction withFIG. 21. The stimulus selection operation may include at least one additional operation, such as an operation3972. The operation3972 includes electronically selecting the modification stimulus from the stimulus or the another stimulus in response to the selected medicament-release state, the selecting the stimulus based on an electronically-stored database relating stimuli and medicament-release state of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state of the final dosage form and stimuli. In an embodiment, the operation3972 may be implemented using thestimulus selection circuit2170 described in conjunction withFIG. 21. In another embodiment, the operation3972 may be implemented using a combination of thestimulus selection circuit2170, thecomputing device2175, and/or the final dosage form andstimulus exposure database2182 described in conjunction withFIG. 21. Themodification operation3920 is described in conjunction withFIG. 49.
• FIG. 51 illustrates anexample environment4000 that includes an article ofmanufacture4001. In an embodiment, the article of manufacture includes thefinal dosage form3702 described in conjunction withFIG. 47. The article of manufacture also includesinstructions4070. The instructions specify an ex vivo exposure of the release element of the final dosage form to the stimulus or an ex vivo exposure of the another release element of the final dosage form to the another stimulus. The instructions when implemented transform the release element to the second medicament-release state or the another release element to the another second medicament-release state.
• FIG. 52 illustrates anexample environment4100 that includes an article ofmanufacture4101. In an embodiment, the article of manufacture includes thefinal dosage form3810 described in conjunction withFIG. 48. The article of manufacture also includesinstructions4170. The instructions specify an ex vivo exposure of the release element of the final dosage form to the stimulus or an ex vivo exposure of the another release element of the final dosage form to the another stimulus. The instructions when implemented transform the release element to the second medicament-release state or the another release element to the another second medicament-release state.
• FIG. 53 illustrates an example article ofmanufacture4202 for administering medicament to an animal. The article includes themedicament190A. The article also includes means4224 for medicament release control in a first state wherein the medicament has a first bioavailability to the animal if the article of manufacture is administered to the animal. The means for medicament release control is modifiable ex vivo to a second state by an exposure to a stimulus, wherein the medicament has a second bioavailability to the animal if the article of manufacture is administered to the animal. The article includes anothermedicament190B. The article also includes another means4264 for medicament release control in another first state wherein the another medicament has another first bioavailability to the animal if the article of manufacture is administered to the animal. The another means for medicament release control is modifiable ex vivo to another second state by an exposure to another stimulus, wherein the another medicament has another second bioavailability to the animal if the article of manufacture is administered to the animal.
• In an embodiment, thearticle4202 includes means4228 for indicating an exposure of the means4224 for medicament release control to thestimulus190A. In an embodiment, the article includes another means4268 for indicating an exposure of the another means4264 for medicament release control to the anotherstimulus190B. In an embodiment, the article includesmeans4280 for protecting the article of manufacture against an ex vivo environment. In an embodiment, the article includesmeans4290 for carrying the article of manufacture into the animal.
• FIG. 54 illustrates anexample environment4300. The environment includes afinal dosage form4310 for administering medicament to theanimal198. The final dosage form includes a dosage portion having a site and a medicament in a first association. The dosage portion is illustrated as “A Dosage Portion,” and illustrates a molecule having a site and the medicament (illustrated below as medicaments190A,190B, and190C) in a first association. In another embodiment, the “A Dosage Portion” may include a large number of molecules each respectfully having a site and an instance of the medicament in a first association. In an embodiment, the site is provided by a gel, illustrated as ahydrogel4302A, and themedicament190A is in a first association with the site. In an embodiment, the site of the dosage portion is provided by a liposome, illustrated as aliposome4302B, and themedicament190B is in a first association with the site. In an embodiment, the site of the dosage portion is provided by a nanoparticle, illustrated as nanosphere4302C and themedicament190C is in a first association with the site. In an embodiment, the site of the dosage portion includes an active site of a molecule. In an embodiment, the site of the dosage portion includes a binding site of a molecule. In an embodiment, the site of the dosage portion includes a site of an intelligent molecule.
• In the first association, the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The first association of the site and the medicament is modifiable ex vivo to a second association of the site and the medicament by an exposure to a stimulus, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal.
• Thefinal dosage form4310 includes another dosage portion having another site and another medicament in another first association. The another dosage portion is illustrated as “Another Dosage Portion,” and illustrates another molecule having another site and the another medicament (illustrated below as medicaments190A,190B, and190C) in another first association. In another embodiment, the “Another Dosage Portion” may include a large number of another molecules each respectfully having another site and an instance of the medicament in another first association. In an embodiment, the another site is provided by a gel, illustrated as ahydrogel4302A, and themedicament190A is in a first association with the another site. In an embodiment, the another site of the another dosage portion is provided by a liposome, illustrated as aliposome4302B, and themedicament190B is in another first association with the another site. In an embodiment, the another site of the another dosage portion is provided by a nanoparticle, illustrated as nanosphere4302C and themedicament190C is in another first association with the another site. In an embodiment, the another site of the another dosage portion includes an active site of another molecule. In an embodiment, the another site of the another dosage portion includes another binding site of another molecule. In an embodiment, the another site of the another dosage portion includes another site of another intelligent molecule.
• In the another first association, the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal. The another first association of the another site and the another medicament is modifiable ex vivo to another second association of the another site and the another medicament by an exposure to another stimulus, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal.
• In an embodiment, the dosage portion and the another dosage portion may be in an unstructured proximity. For example, the dosage portion and the another dosage portion may be dispersed or suspended in a solid transport medium, a liquid transport medium, a gel transport medium, or a solid transport medium. In another embodiment, the dosage portion and the another dosage portion may be in a structured relationship in a solid transport medium, a liquid transport medium, a gel transport medium, or a solid transport medium.
• In an embodiment, the dosage portion includes a particle. In an embodiment, the dosage portion includes a polymeric material. In an embodiment, the another dosage portion includes another particle. In an embodiment, the site and the medicament in a first association includes a site of a particle or polymeric material in a first association with the medicament. In an embodiment, the site and the medicament in a first association includes a site of a particle or polymeric material encapsulating the medicament and in a first association with the medicament. In an embodiment, the site and the medicament in a first association includes a particle or polymeric material site that at least one of engages, retains, or binds the medicament in a first association. In an embodiment, the another dosage portion includes another polymeric material.
• In an embodiment, the first bioavailability to theanimal198 includes the medicament is not bioavailable to the animal. In an embodiment, the first bioavailability to the animal includes the medicament is bioavailable to the animal. In an embodiment, the second bioavailability to the animal includes the medicament is not bioavailable to the animal. In an embodiment, the second bioavailability to the animal includes the medicament is bioavailable to the animal. In an embodiment, the another first bioavailability to the animal includes the another medicament is not bioavailable to the animal. In an embodiment, the another first bioavailability to the animal includes the another medicament is bioavailable to the animal. In an embodiment, the another second bioavailability to the animal includes the another medicament is not bioavailable to the animal. In an embodiment, the another second bioavailability to the animal includes the another second medicament is bioavailable to the animal.
• In an embodiment, the first bioavailability to the animal includes a first bioavailability characteristic and the second bioavailability to the animal includes a second bioavailability characteristic. In an embodiment, the another first bioavailability to the animal includes another first bioavailability characteristic and the another second bioavailability to the animal includes another second bioavailability characteristic.
• In an embodiment, the stimulus includes at least one of a mechanical stimulus, a non-ionizing radiation stimulus, an ionizing radiation stimulus, a chemical stimulus, an acoustic stimulus, an ultrasound stimulus, a radio wave stimulus, a microwave stimulus, a light wave stimulus, or a thermal stimulus. In an embodiment, the another stimulus includes at least one of a mechanical stimulus, a non-ionizing radiation stimulus, an ionizing radiation stimulus, a chemical stimulus, an acoustic stimulus, an ultrasound stimulus, a radio wave stimulus, a microwave stimulus, a light wave stimulus, or a thermal stimulus.
• FIG. 54 illustrates another embodiment of the final dosage form4130 for administering medicament to theanimal198. In this another embodiment, in the first association of site and the medicament, the medicament is substantially not bioavailable to theanimal198 if the final dosage form4130 is administered to the animal. The first association of the site and the medicament is modifiable ex vivo to a second association by an exposure to a stimulus of thestimulus192, wherein the medicament is substantially bioavailable to the animal if the final dosage form is administered to the animal.
• In this another embodiment, in the another first association of the another site and the another medicament, the another medicament is substantially not bioavailable to theanimal198 if the final dosage form4130 is administered to the animal. The another first association of the another site and the another medicament is modifiable ex vivo to another second association by an exposure to another stimulus, wherein the another medicament is substantially bioavailable to the animal if the final dosage form is administered to the animal.
• FIG. 55 illustrates anexample environment4400 that includes afinal dosage form4405 and anoperational flow4420. Thefinal dosage form4405 is substantially similar to thefinal dosage form4310 described in conjunction withFIG. 54.
• After a start operation, the operational flow includes acustomization operation4420. The customization operation includes transforming the final dosage form into a selected medicament release state by initiating an ex vivo exposure of the first association of the site and the medicament or the another first association of the another site and the another medicament to a modification stimulus respectfully selected from the stimulus or the another stimulus. The operational flow includes an end operation.
• In an embodiment, thecustomization operation4420 may include at least one additional operation, such as an operation4422. The operation4422 includes transforming the final dosage form into a selected medicament release state by initiating an ex vivo exposure of the first association of the site and the medicament and the another first association of the another site and the another medicament to the stimulus and the another stimulus. In an embodiment, theoperational flow4420 may be implemented using thesystem2100 described in conjunction withFIG. 27.
• FIG. 56 illustrates an alternative embodiment of theoperational flow4420 described inFIG. 55. In an embodiment, the operational flow may include at least one additional operation. The at least one additional operation may include a treatment-order operation4450, a release-state selection operation4460, or a modification-stimulus selection operation4470. The treatment-order operation includes receiving a signal indicative of a chosen medicament bioavailability of thefinal dosage form4405. The treatment-order operation may be implemented using thesystem2100 described in conjunction withFIG. 27. In an embodiment, the treatment-order operation may include at least one additional operation. The at least one additional operation may include anoperation4452 or anoperation4454. Theoperation4452 includes receiving a machine-initiated signal indicative of the chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation4452 may be implemented using the other circuit(s)2190 to receive data, an email or fax indicative of the chosen medicament bioavailability of the final dosage form. Theoperation4454 includes receiving a signal responsive to human-initiated indication of the chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation4454 may be implemented using theuser interface2195 ofFIG. 27 to receive a human-initiated input by theperson2199.
• The release-state selection operation4460 includes selecting a medicament-release state of the site and the medicament or of the another site and the another medicament in response to the chosen medicament-bioavailability of the final dosage form. In an embodiment, the release-state selection operation may be implemented using the release-state selection circuit2165 ofFIG. 27. In an embodiment, the release-state selection operation may be implemented using the release-state selection circuit2165 and a human2199 initiated input entered into theuser interface2195. The release-state selection operation may include at least one additional operation, such as an operation4462. The operation4462 includes electronically selecting a medicament-release state of the site and the medicament or of the another site and the another medicament in response to the chosen medicament-bioavailability of the final dosage form, the selecting a medicament-release state based on an electronically-stored database relating medicament-release state and medicament-bioavailability of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state and medicament-bioavailability of the final dosage form. In an embodiment, the operation4462 may be implemented using the release-state selection circuit2165. In an embodiment, the operation4462 may be implemented using the release-state selection circuit, thecomputing device2175, and/or the final dosage form and stimulus exposure database2182 (saved on the computer-readable storage medium2180).
• The modification-stimulus selection operation4470 includes selecting the modification-stimulus from the stimulus or the another stimulus in response to the selected medicament-release state. In an embodiment, modification-stimulus selection operation may be implemented using thestimulus selection circuit2170 described in conjunction withFIG. 27. The modification-stimulus selection operation may include at least one additional operation, such as the operation4472. The operation4472 electronically selecting the modification-stimulus from the stimulus or the another stimulus in response to the selected medicament-release state, the selecting the modification-stimulus based on an electronically-stored database relating stimuli and medicament-release state of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state of the final dosage form and stimuli. In an embodiment, the stimulus selection circuit, thecomputing device2175, and/or the final dosage form andstimulus exposure database2182 may cooperatively implement the operation4472.
• FIG. 57 illustrates anexample environment4500. The environment includes an article ofmanufacture4501. In an embodiment, the article of manufacture includes thefinal dosage form4310 described in conjunction withFIG. 54. The article of manufacture includesinstructions4570 specifying an ex vivo exposure of the first association of the site and the medicament to the stimulus or an ex vivo exposure of the another first association of the another site and the another medicament to the another stimulus. The ex vivo exposure if implemented transforms the first association of the site and the medicament to the second association or the another first association of the another site and the another medicament to the another second association.
• FIG. 58 illustrates an example article ofmanufacture4602 for administering medicament to an animal. The article includesmeans4624 for encapsulating amedicament190A in a first medicament-release state. In the first medicament-release state, medicament has a first bioavailability to the animal if the article of manufacture is administered to the animal in the first medicament-release state. The means for encapsulating a medicament in a first medicament-release state is modifiable ex vivo to a second medicament-release state by an exposure to a stimulus, wherein the medicament has a second bioavailability to the animal if the article of manufacture is administered to the animal in the second medicament-release state. The article of manufacture also includes themedicament190A.
• The article ofmanufacture4602 includes another means4664 for encapsulating anothermedicament190B in another first medicament-release state. In the another first medicament-release state, the another medicament has another first bioavailability to the animal if the article of manufacture is administered to the animal in the another first medicament-release state. The another means for encapsulating another medicament is modifiable ex vivo to another second medicament-release state by an exposure to another stimulus, wherein the another medicament has another second bioavailability to the animal if the article of manufacture is administered to the animal in the another second medicament-release state. The article of manufacture also includes themedicament190B.
• In an embodiment, the article of manufacture may include means4628 for indicating an exposure of the means for encapsulating a medicament in a first medicament-release state to the stimulus. In an embodiment, the article of manufacture may include another means4668 for indicating an exposure of the another means for encapsulating another medicament in another first medicament-release state to the another stimulus. In an embodiment, the article of manufacture may includemeans4680 for protecting the article of manufacture against an ex vivo environment. In an embodiment, the article of manufacture may include means4590 for carrying the article of manufacture into the animal.
• FIG. 59 illustrates anexample environment4700. The environment includes afinal dosage form4710 for administering medicament to theanimal198. The final dosage form includes a dosage portion, illustrated as “A Dosage Portion,” that includes a substance associated with a medicament (illustrated and described below as medicaments190A,190B, and190C) in a first release-control state. In an embodiment, the “A Dosage Portion” may include a large number of substances each respectfully associated with an instance of the medicament in a first release-control state.
• In an embodiment, the substance includes a gel, illustrated as ahydrogel4702A, associated with themedicament190A in a first release-control state. In an embodiment, the substance includes a liposome, illustrated as aliposome4702B, associated with themedicament190B in a first release-control state. In an embodiment, the substance includes a nanoparticle, illustrated asnanosphere4702C associated with themedicament190C in a first release-control state. In an embodiment, the substance includes an active site of a molecule associated with the medicament in a first release-control state. In an embodiment, the substance includes a molecule associated with the medicament in a first release-control state. In an embodiment, the substance includes an intelligent molecule associated with the medicament in a first release-control state.
• In the first release control state, the medicament has a first bioavailability to theanimal198 if thefinal dosage form4710 is administered to the animal. The substance associated with the medicament in a first release-control state is modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state. In the second release-control state, the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal.
• Thefinal dosage form4710 includes another dosage portion, illustrated as “Another Dosage Portion,” that includes another substance associated with another medicament (illustrated and described as medicaments190A,190B, and190C) in another first release-control state. In an embodiment, the “Another Dosage Portion” may include a large number of another substances each respectfully associated with an instance of the another medicament in another first release-control state.
• In an embodiment, the another substance includes another gel, illustrated as ahydrogel4702A, associated with the anothermedicament190A in another first release-control state. In an embodiment, the another substance includes another liposome, illustrated as aliposome4702B, associated with the anothermedicament190B in another first release-control state. In an embodiment, the another substance includes another nanoparticle, illustrated asnanosphere4702C associated with the anothermedicament190C in another first release-control state. In an embodiment, the another substance includes an active site of another molecule associated with the another medicament in another first release-control state. In an embodiment, the another substance includes another molecule associated with the medicament in a first release-control state. In an embodiment, the another substance includes another intelligent molecule associated with the another medicament in another first release-control state.
• In the another first release control state, the another medicament has another first bioavailability to theanimal198 if thefinal dosage form4710 is administered to the animal. The another substance associated with the another medicament in a first release-control state is modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state. In the second release-control state, the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal.
• In an embodiment, the dosage portion and the another dosage portion may be in an unstructured proximity, and not necessarily physically distinct structures. For example, the dosage portion and the another dosage portion may be dispersed or suspended in a solid transport medium, a liquid transport medium, a gel transport medium, or a solid transport medium. In another embodiment, the dosage portion and the another dosage portion may be in a structured relationship in a solid transport medium, a liquid transport medium, a gel transport medium, or a solid transport medium.
• In an embodiment, the substance associated with the medicament in a first release-control state includes a particle associated with the medicament in a first release-control state. In an embodiment, the substance associated with the medicament in a first release-control state includes a polymeric material associated with the medicament in a first release-control state. In an embodiment, the substance associated with the medicament in a first release-control state includes a small molecule associated with the medicament in a first release-control state. In an embodiment, the substance associated with the medicament in a first release-control state includes an intelligent molecule associated with the medicament in a first release-control state. In an embodiment, the substance associated with the medicament in a first release-control state includes an encapsulating substance associated with the medicament in a first release-control state. In an embodiment, the substance associated with the medicament in a first release-control state includes a conjugating substance joined with the medicament in a first release-control state. In an embodiment, the substance associated with the medicament in a first release-control state includes a binding substance bound with the medicament in a first release-control state. In an embodiment, the substance associated with the medicament in a first release-control state includes a substance at least one of engaging, or retaining the medicament in a first release-control state.
• In an embodiment, the first bioavailability includes a first bioavailability characteristic and the second bioavailability includes a second bioavailability characteristic. In an embodiment, the first bioavailability to the animal includes the medicament being substantially not bioavailable to the animal. In an embodiment, the first bioavailability to the animal includes the medicament being substantially bioavailable to the animal. In an embodiment, the second bioavailability to the animal includes the medicament being substantially not bioavailable to the animal. In an embodiment, the second bioavailability to the animal includes the medicament being substantially bioavailable to the animal. In an embodiment, the second bioavailability to the animal includes the medicament being substantially bioavailable to the animal, wherein the second bioavailability to the animal is substantially different than the first bioavailability to the animal.
• FIG. 59 also illustrates an alternative embodiment of theexample environment4700. The alternative embodiment of environment includes an alternative embodiment of thefinal dosage form4710 for administering medicament to theanimal198. The final dosage form includes a dosage portion, illustrated as “A Dosage Portion,” that includes a substance associated with a medicament (illustrated and described below as medicaments190A,190B, and190C) in a first state. In an embodiment, the “A Dosage Portion” may include a large number of substances each respectfully associated with an instance of the medicament in a first state.
• In an embodiment, the substance includes a gel, illustrated as ahydrogel4702A, associated with themedicament190A in a first state. In an embodiment, the substance includes a liposome, illustrated as aliposome4702B, associated with themedicament190B in a first state. In an embodiment, the substance includes a nanoparticle, illustrated asnanosphere4702C associated with themedicament190C in a first state. In an embodiment, the substance includes an active site of a molecule associated with the medicament in a first state. In an embodiment, the substance includes a molecule associated with the medicament in a first state. In an embodiment, the substance includes an intelligent molecule associated with the medicament in a first state.
• In the first state, the medicament has a first bioavailability to theanimal198 if thefinal dosage form4710 is administered to the animal. The substance associated with the medicament in a first state is modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second state. In the second state, the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal.
• Thefinal dosage form4710 includes another dosage portion, illustrated as “Another Dosage Portion,” that includes another substance associated with another medicament (illustrated and described as medicaments190A,190B, and190C) in another first state. In an embodiment, the “Another Dosage Portion” may include a large number of another substances each respectfully associated with an instance of the another medicament in another first state.
• In an embodiment, the another substance includes another gel, illustrated as ahydrogel4702A, associated with the anothermedicament190A in another first state. In an embodiment, the another substance includes another liposome, illustrated as aliposome4702B, associated with the anothermedicament190B in another first state. In an embodiment, the another substance includes another nanoparticle, illustrated asnanosphere4702C associated with the anothermedicament190C in another first state. In an embodiment, the another substance includes an active site of another molecule associated with the another medicament in another first state. In an embodiment, the another substance includes another molecule associated with the medicament in a first state. In an embodiment, the another substance includes another intelligent molecule associated with the another medicament in another first state.
• In the another first state, the another medicament has another first bioavailability to theanimal198 if thefinal dosage form4710 is administered to the animal. The another substance associated with the another medicament in a first state is modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second state. In the second state, the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal.
• FIG. 60 illustrates anexample environment4800 that includes afinal dosage form4805 for administering medicament to an animal and anoperational flow4820. The final dosage form includes a medicament. The final dosage form also includes a substance associated with the medicament in a first release-control state. In the first release-control state, the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The substance is modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state. In the second release-control state, the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. The final dosage form also includes another medicament. The final dosage form includes another substance associated with the another medicament in another first release-control state. In the another first release-control state, the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal. The another substance is modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal. In an embodiment, thefinal dosage form4805 is substantially similar to thefinal dosage form4710 previously described in conjunction withFIG. 59.
• After a start operation, theoperational flow4810 includes acustomization operation4820. The customization operation includes transforming thefinal dosage form4805 into a selected medicament release state by initiating an ex vivo exposure of the substance associated with the medicament in a first release-control state or an ex vivo exposure of the another substance associated with the another medicament in another first release-control state to a modification stimulus respectfully selected from the stimulus or the another stimulus. The operational flow includes an end operation. In an embodiment, theoperational flow4810 may be implemented using thesystem2100 described in conjunction withFIG. 27.
• In an alternative embodiment, theoperational flow4810 may include at least one additional operation, such as an operation4822. The operation4822 includes transforming the final dosage form into a selected medicament release state by initiating an ex vivo exposure of the substance associated with the medicament in a first release-control state and an ex vivo exposure of the another substance associated with the another medicament in another first release-control state to the stimulus and the another stimulus.
• FIG. 61 illustrates an alternative embodiment of theoperational flow4805 described in conjunction withFIG. 60. In an embodiment, the operational flow may include at least one additional operation. The at least one additional operation may include a treatment-order operation4850, a release-state selection operation4860, or a modification-stimulus selection operation4870. The treatment-order operation includes receiving a signal indicative of a chosen medicament bioavailability of the final dosage form. The treatment-order operation may be implemented using thesystem2100 described in conjunction withFIG. 27. The treatment-order operation may include at least one additional operation. The at least one additional operation may include anoperation4852 or anoperation4854. Theoperation4852 includes receiving a machine-initiated signal indicative of a chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation4852 may be implemented using the other circuit(s)2190 to receive data, an email or fax indicative of the chosen medicament bioavailability of the final dosage form. Theoperation4854 includes receiving a human-initiated a signal indicative of a chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation4854 may be implemented using theuser interface2195 ofFIG. 27 to receive a human-initiated input by theperson2199.
• The release-state selection operation4860 includes selecting the medicament-release state of the substance associated with the medicament or of the another substance associated with the another medicament in response to the chosen medicament-bioavailability of the final dosage form. In an embodiment, the release-state selection operation may be implemented using the release-state selection circuit2165 ofFIG. 27. In an embodiment, the release-state selection operation may be implemented using the release-state selection circuit2165 and a human2199 initiated input entered into theuser interface2195. In an embodiment, the release-state selection operation may include at least one additional operation, such as an operation4862. The operation4862 includes electronically selecting the medicament-release state of the substance associated with the medicament or of the another substance associated with the another medicament in response to the chosen medicament-bioavailability of the final dosage form. The selecting a medicament-release state is based on an electronically-stored database relating medicament-release state and medicament-bioavailability of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state and medicament-bioavailability of the final dosage form. In an embodiment, the operation4862 may be implemented using the release-state selection circuit2165. In an embodiment, the operation4862 may be implemented using the release-state selection circuit, thecomputing device2175, and/or the final dosage form and stimulus exposure database2182 (saved on the computer-readable storage medium2180).
• The modification-stimulus selection operation4870 includes selecting the modification-stimulus from the stimulus or the another stimulus in response to the selected medicament-release state. In an embodiment, modification-stimulus selection operation may be implemented using thestimulus selection circuit2170 described in conjunction withFIG. 27. The modification-stimulus selecting operation may include at least one additional operation, such as the operation4872. The operation4872 includes electronically selecting the modification-stimulus from the stimulus or the another stimulus in response to the selected medicament-release state, the selecting the stimulus based on an electronically-stored database relating stimuli and medicament-release state of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state of the final dosage form and stimuli. In an embodiment, the stimulus selection circuit, thecomputing device2175, and/or the final dosage form andstimulus exposure database2182 may cooperatively implement the operation4872. Thecustomization operation4820 is described in conjunction withFIG. 60.
• FIG. 62 illustrates an example article ofmanufacture4902 for administering medicament to an animal. The article of manufacture includes themedicament190A. The article of manufacture also includes an intelligentmolecular means4924 associated with the medicament in a first release-control state. In the first release-control state, the medicament has a first bioavailability to the animal if the article of manufacture is administered to the animal. The intelligent molecular means is modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state. In the second release-control state, the medicament has a second bioavailability to the animal if the article of manufacture is administered to the animal.
• The article ofmanufacture4902 includes the anothermedicament190B. The article of manufacture also include another intelligentmolecular means4964 associated with the another medicament in another first release-control state. In the another first release-control state, the another medicament has another first bioavailability to the animal if the article of manufacture is administered to the animal. The another intelligent molecular means is modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state. In the another second release-control state, the another medicament has another second bioavailability to the animal if the article of manufacture is administered to the animal.
• In an embodiment, the article ofmanufacture4902 includes means4928 for indicating an exposure to the stimulus of the intelligent molecular means associated with a medicament in a first medicament-release state. In an embodiment, the article of manufacture includes another means4968 for indicating an exposure to the another stimulus of the another intelligent molecular means associated with another medicament in another first medicament-release state. In an embodiment, the article of manufacture includesmeans4980 for protecting the article of manufacture against an ex vivo environment. In an embodiment, the article of manufacture includesmeans4990 for carrying the article of manufacture into the animal.
• FIG. 63 illustrates anexample environment5000. The environment includes afinal dosage form5010 for administering medicament to theanimal198. The final dosage form includes at least two respective instances of a medicament and a substance, illustrated asinstances5002.
• Thefinal dosage form5010 includes an instance5002.1 of a substance carrying a medicament in a first medicament-release state. In an embodiment, the instance5002.1 may include a large number of substances each respectfully carrying the medicament in a first medicament-release state. In an embodiment, the substance includes a gel, illustrated as ahydrogel5002A, carrying themedicament190A in a first medicament-release state. In an embodiment, the substance includes a liposome, illustrated as aliposome5002B, carrying themedicament190B in a first medicament-release state. In an embodiment, the substance includes a nanoparticle, illustrated asnanosphere5002C carrying themedicament190C in a first medicament-release state. In an embodiment, the substance includes an active site of a molecule carrying the medicament in a first medicament-release state. In an embodiment, the substance includes a molecule carrying the medicament in a first medicament-release state. In an embodiment, the substance includes an intelligent molecule carrying the medicament in a first medicament-release state.
• The medicament has a first bioavailability to theanimal198 if thefinal dosage form5010 is administered to the animal. The substance is modifiable ex vivo by an exposure to a first stimulus to carry the medicament in a second medicament-release state. In the second medicament-release state, the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal. The substance is modifiable ex vivo by an exposure to a second stimulus to carry the medicament in a third medicament-release state. In the third medicament-release state, the medicament has a third bioavailability to the animal if the final dosage form is administered to the animal.
• Thefinal dosage form5010 includes another instance5002.2 of another substance carrying another medicament in another first medicament-release state. In an embodiment, the another instance5002.2 may include a large number of another substances each respectfully carrying the another medicament in another first medicament-release state. In an embodiment, the another substance includes a gel, illustrated as ahydrogel5002A, carrying the anothermedicament190A in another first medicament-release state. In an embodiment, the another substance includes a liposome, illustrated as aliposome5002B, carrying the anothermedicament190B in another first medicament-release state. In an embodiment, the another substance includes another nanoparticle, illustrated asnanosphere5002C carrying the anothermedicament190C in another first medicament-release state. In an embodiment, the another substance includes another active site of another molecule carrying the another medicament in another first medicament-release state. In an embodiment, the another substance includes another molecule carrying the another medicament in another first medicament-release state. In an embodiment, the another substance includes another intelligent molecule carrying the another medicament in another first medicament-release state.
• The another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal. The another substance is modifiable ex vivo by an exposure to another first stimulus to carry the another medicament in another second medicament-release state. In the another second medicament-release state, the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal. The another substance is modifiable ex vivo by an exposure to another second stimulus to carry the another medicament in another third medicament-release state. In the another third medicament-release state, the another medicament has another third bioavailability to the animal if the final dosage form is administered to the animal.
• In an embodiment, thesubstance5002 carrying the medicament in a first medicament-release state includes a substance having a modifiable medicament release characteristic and carrying the medicament in a first medicament-release state. In an embodiment, the substance carrying the medicament in a first medicament-release state includes a substance carrying the medicament in an initial medicament-retention state. In an embodiment, the substance carrying the medicament in a first medicament-release state includes a particle carrying the medicament in a first medicament-release state. In an embodiment, the substance carrying the medicament in a first medicament-release state includes a polymeric material carrying the medicament in a first medicament-release state. In an embodiment, the substance carrying the medicament in a first medicament-release state includes a small molecule carrying the medicament in a first medicament-release state. In an embodiment, the substance carrying the medicament in a first medicament-release state includes a capsule structure carrying the medicament in a first medicament-release state.
• In an embodiment, the medicament has a first bioavailability to the animal includes the medicament is not bioavailable to the animal. In an embodiment, the medicament has a first bioavailability to the animal includes the medicament is bioavailable to the animal. In an embodiment, the medicament has a second bioavailability to the animal includes the medicament is not bioavailable to the animal. In an embodiment, the medicament has a second bioavailability to the animal includes the medicament is bioavailable to the animal. In an embodiment, the medicament has a third bioavailability to the animal includes the medicament is not bioavailable to the animal. In an embodiment, the medicament has a third bioavailability to the animal includes the medicament is bioavailable to the animal.
• In an embodiment, the another medicament has another first bioavailability to the animal includes the another medicament is not bioavailable to the animal. In an embodiment, the another medicament has another first bioavailability to the animal includes the another medicament is bioavailable to the animal. In an embodiment, the another medicament has another second bioavailability to the animal includes wherein the another medicament is not bioavailable to the animal. In an embodiment, the another medicament has another second bioavailability to the animal includes the another medicament is bioavailable to the animal. In an embodiment, the another medicament has another third bioavailability to the animal includes the another medicament is not bioavailable to the animal. In an embodiment, the another medicament has another third bioavailability to the animal includes the another medicament is bioavailable to the animal. In an embodiment, the first bioavailability includes a first bioavailability characteristic, the second bioavailability includes a second bioavailability characteristic, and the third bioavailability includes a third bioavailability characteristic.
• Theexample environment5000 ofFIG. 63 illustrates another embodiment of thefinal dosage form5010 for administering medicament to theanimal198. The final dosage form includes at least two instances of a medicament and a substance, illustrated asinstances5002.
• Thefinal dosage form5010 includes an instance5002.1 of a substance carrying a medicament in a medicament-retention state. The medicament is substantially not bioavailable to the animal if the final dosage form is administered to the animal. The substance is modifiable ex vivo by an exposure to a first stimulus to carry the medicament in a first medicament-release state. In the first medicament-release state, the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal. The substance is modifiable ex vivo by an exposure to a second stimulus to carry the medicament in a second medicament-release state. In the second medicament-release state, the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal.
• Thefinal dosage form5010 includes another instance5002.2 of another substance carrying another medicament in another medicament-retention state. The another medicament is substantially not bioavailable to the animal if the final dosage form is administered to theanimal198. The another substance is modifiable ex vivo by an exposure to another first stimulus to carry the another medicament in another first medicament-release state. In the another first medicament-release state, the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal. The another substance is modifiable ex vivo by an exposure to another second stimulus to carry the another medicament in another second medicament-release state. In the another second medicament-release state, the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal.
• The following table illustrates several states of example embodiments of the final dosage form5010:

• TABLE 4
  Example bioavailability configurations

  	Example Configuration #1	Example Configuration #2
  	Bioavailability	Bioavailability

  Substance

  1	Substance 2	Substance 1	Substance 2
  	(100 mg	(200 mg TR	(100 mg	(200 mg
  State of substance	medicament A)	medicament A)	medicament A)	medicament B)
  State 1	0	0	1	0
  (initial)
  State 2	1	0	0	0
  (first stimulus to Substance 1)
  State 3	2	0	2	0
  (second stimulus to Substance 1)
  State 4	0	1	1	1
  (another first stimulus to
  Substance 2)
  State 4	0	2	1	2
  (another second stimulus to
  Substance 2)
  State 5	1	1	0	1
  (first stimulus toSubstance 1,
  and another first stimulus to
  Substance 2)
  State 6	2	1	2	1
  (second stimulus toSubstance 1,
  and another first stimulus to
  Substance 2)
  State 7	1	2	0	2
  (first stimulus toSubstance 1,
  and another second stimulus to
  Substance 2)
  State 8	2	2	1	2
  (second stimulus toSubstance 1,
  and another second stimulus to
  Substance 2)
  0 = medicament is substantially not bioavailable
  1 = medicament is bioavailable
  2 = medicament is bioavailable in a substantially different characteristic than inbioavailability 1

• FIG. 64 illustrates anexample environment5100. The environment includes afinal dosage form5110 for administering medicament to theanimal198. An element of the final dosage form is illustrated as an element5102.1. Another element of the final dosage includes another element5102.2 (not shown). The element and the another element may be included in a transport medium (not shown) of the final dosage form. The transport medium may include a carrier, admixture, diluent, or excipient.
• In an embodiment, the element5102.1 of thefinal dosage form5110 includes an “A Dosage Portion” that is substantially similar tofinal dosage form102 described in conjunction withFIG. 1, and a “Another Dosage Portion” that is substantially similar tofinal dosage form302 described in conjunction withFIG. 3. The element5102.1 of thefinal dosage form5110 includes a medicament, illustrated in “A Dosage Portion” as themedicament190A, and a medicament, illustrated in “Another Dosage Portion” as themedicament190B. The element5102.1 carries themedicament190A in a first medicament-release state. In the first medicament-release state, themedicament190A has a first bioavailability to theanimal198 if the final dosage form is administered to the animal. The element5102.1 is modifiable ex vivo by an exposure to a first stimulus to carry themedicament190A in a second medicament-release state. In the second medicament-release state, themedicament190A has a second bioavailability to the animal if the final dosage form is administered to the animal.
• The element5102.1 carries themedicament190B in the “B Dosage Portion” in the first medicament-release state. In the first medicament-release state, themedicament190B has a first bioavailability to theanimal198 if the final dosage form is administered to the animal. The “Another Dosage Portion” of element5102.1 is modifiable ex vivo by an exposure to a second stimulus to carry themedicament190B in a third medicament-release state. In the third medicament-release state, the medicament has a third bioavailability to the animal if the final dosage form is administered to the animal.
• In an embodiment, the element5102.2 includes another medicament having release states modifiable ex vivo in a manner substantially similar to the element5102.1.
• FIG. 65 illustrates anexample environment5200. The environment includes afinal dosage form5205 and anoperational flow5220. In an embodiment, the final dosage form is substantially similar to thefinal dosage form5010 described in conjunction withFIG. 63. In another embodiment, the final dosage form is substantially similar to thefinal dosage form5110 described in conjunction withFIG. 64.
• After a start operation, theoperational flow5210 includes acustomization operation5220. The customization operation includes transforming thefinal dosage form5205 into a selected medicament-release state by initiating an ex vivo exposure to a modification stimulus of the substance carrying the medicament in a first medicament-release state or the another substance carrying the another medicament in another first medicament-release state. The modification stimulus is respectfully selected from the first stimulus or the second stimulus for the substance, or from the another first stimulus or the another second stimulus for the another substance. The operational flow includes an end operation. In an embodiment, theoperational flow5210 may be implemented using thesystem2100 described in conjunction withFIG. 27.
• In an embodiment, thecustomization operation5220 may include at least one additional operation, such as an operation5222. The operation5222 includes transforming thefinal dosage form5205 into a selected medicament-release state by initiating an ex vivo exposure to a modification stimulus of the substance carrying the medicament in a first medicament-release state and the another substance carrying the another medicament in another first medicament-release state. The modification stimulus includes a stimulus selected from the first stimulus or the second stimulus for the substance, and another stimulus selected from the another first stimulus or the another second stimulus for the another substance.
• FIG. 66 illustrates an alternative embodiment of theoperational flow5210 described in conjunction withFIG. 65. In an embodiment, the operational flow may include at least one additional operation. The at least one additional operation may include a treatment-order operation5250, a release-state selection operation5260, or a modification-stimulus selection operation5270. The treatment order operation includes receiving a signal indicative of a chosen medicament bioavailability of the final dosage form. The treatment-order operation may be implemented using thesystem2100 described in conjunction withFIG. 27. The treatment-order operation may include at least one additional operation. The at least one additional operation may include anoperation5252 or anoperation5254. Theoperation5252 includes receiving a machine-initiated signal indicative of a chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation5252 may be implemented using the other circuit(s)2190 to receive data or an email or fax indicative of the chosen medicament bioavailability of the final dosage form. Theoperation5254 includes receiving a human-initiated signal indicative of the chosen medicament bioavailability of the final dosage form. In an embodiment, theoperation5254 may be implemented using theuser interface2195 ofFIG. 27 to receive a human-initiated input by theperson2199.
• The release-state selection operation5260 includes selecting the medicament-release state of the substance or of the another substance in response to the chosen medicament-bioavailability of the final dosage form. In an embodiment, the release-state selection operation may be implemented using the release-state selection circuit2165 ofFIG. 27. In an embodiment, the release-state selection operation may be implemented using the release-state selection circuit2165 and a human2199 initiated input entered into theuser interface2195. In an embodiment, the release-state selection operation may include at least one additional operation, such as an operation5262. The operation5262 includes electronically selecting the medicament-release state of the substance or of the another substance in response to the chosen medicament-bioavailability of the final dosage form. The selecting a medicament-release state is based on an electronically-stored database relating medicament-release state and medicament-bioavailability of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state and medicament-bioavailability of the final dosage form. In an embodiment, the operation5262 may be implemented using the release-state selection circuit2165. In an embodiment, the operation5262 may be implemented using the release-state selection circuit, thecomputing device2175, and/or the final dosage form and stimulus exposure database2182 (saved on the computer-readable storage medium2180).
• The modification-stimulus selection operation5270 includes selecting the modification-stimulus from the first stimulus, the second stimulus, the another first stimulus or the another second stimulus in response to the selected medicament-release state. In an embodiment, modification-stimulus selection operation may be implemented using thestimulus selection circuit2170 described in conjunction withFIG. 27. In an embodiment, the stimulus selection circuit, thecomputing device2175, and/or the final dosage form andstimulus exposure database2182 may cooperatively implement theoperation5270. The modification-stimulus selecting operation may include at least one additional operation, such as the operation5272. The operation5272 includes electronically selecting the modification stimulus in response to the selected medicament-release state. The selecting the modification stimulus is based on an electronically-stored database relating stimuli and medicament-release state of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state of the final dosage form and stimuli. Thecustomization operation5220 is described in conjunction withFIG. 65.
• FIG. 67 illustrates an example article ofmanufacture5702 for administering medicament to an animal. The article of manufacture includes amedicament190A. The article of manufacture also includes intelligent molecular5724 means associated with the medicament in a first medicament-release state wherein the medicament has a first bioavailability to the animal if the article of manufacture is administered to the animal. The intelligent molecular means is modifiable ex vivo by an exposure to a first stimulus to carry the medicament in a second medicament-release state. In the second medicament-release state, the medicament has a second bioavailability to the animal if the article of manufacture is administered to the animal. The intelligent molecular means is modifiable ex vivo by an exposure to a second stimulus to carry the medicament in a third medicament-release state. In the third medicament-release state, the medicament has a third bioavailability to the animal if the article of manufacture is administered to the animal.
• The article of manufacture includes anothermedicament190B. The article of manufacture also includes another intelligentmolecular means5764 associated with the another medicament in another first medicament-release state wherein the another medicament has another first bioavailability to the animal if the article of manufacture is administered to the animal. The another intelligent molecular means is modifiable ex vivo by an exposure to another first stimulus to carry the another medicament in another second medicament-release state. In another second medicament-release state, the another medicament has another second bioavailability to the animal if the article of manufacture is administered to the animal. The another intelligent molecular means is modifiable ex vivo by an exposure to another second stimulus to carry the another medicament in another third medicament-release state. In another third medicament-release state, the another medicament has another third bioavailability to the animal if the article of manufacture is administered to the animal.
• All references cited herein are hereby incorporated by reference in their entirety or to the extent their subject matter is not inconsistent herewith.
• In some embodiments, “configured” includes at least one of designed, set up, shaped, implemented, constructed, or adapted for at least one of a particular purpose, application, or function.
• It will be understood that, in general, terms used herein, and especially in the appended claims, are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of introductory phrases such as “at least one” or “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to inventions containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a receiver” should typically be interpreted to mean “at least one receiver”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, it will be recognized that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of “at least two chambers,” or “a plurality of chambers,” without other modifiers, typically means at least two chambers).
• Use of “Start,” “End” or “Stop” blocks in the block diagrams is not intended to indicate a limitation on the beginning or end of any functions in the diagram. Such flowcharts or diagrams may be incorporated into other flowcharts or diagrams where additional functions are performed before or after the functions shown in the diagrams of this application.
• In those instances where a phrase such as “at least one of A, B, and C,” “at least one of A, B, or C,” or “an [item] selected from the group consisting of A, B, and C,” is used, in general such a construction is intended to be disjunctive (e.g., any of these phrases would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B, and C together, and may further include more than one of A, B, or C, such as A₁, A₂, and C together, A, B₁, B₂, C₁, and C₂together, or B₁and B₂together). It will be further understood that virtually any disjunctive word or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”
• The herein described aspects depict different components contained within, or connected with, different other components. It is to be understood that such depicted architectures are merely examples, and that in fact many other architectures can be implemented which achieve the same functionality. In a conceptual sense, any arrangement of components to achieve the same functionality is effectively “associated” such that the desired functionality is achieved. Hence, any two components herein combined to achieve a particular functionality can be seen as “associated with” each other such that the desired functionality is achieved, irrespective of architectures or intermedial components. Likewise, any two components so associated can also be viewed as being “operably connected,” or “operably coupled,” to each other to achieve the desired functionality. Any two components capable of being so associated can also be viewed as being “operably couplable” to each other to achieve the desired functionality. Specific examples of operably couplable include but are not limited to physically mateable or physically interacting components or wirelessly interactable or wirelessly interacting components.
• With respect to the appended claims the recited operations therein may generally be performed in any order. Also, although various operational flows are presented in a sequence(s), it should be understood that the various operations may be performed in other orders than those which are illustrated, or may be performed concurrently. Examples of such alternate orderings may include overlapping, interleaved, interrupted, reordered, incremental, preparatory, supplemental, simultaneous, reverse, or other variant orderings, unless context dictates otherwise. Furthermore, terms like “responsive to,” “related to,” or other past-tense adjectives are generally not intended to exclude such variants, unless context dictates otherwise.
• While various aspects and embodiments have been disclosed herein, the various aspects and embodiments are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.

Claims (26)

1. A final dosage form for administering medicament to an animal, the final dosage form including

a medicament;

a substance associated with the medicament in a first release-control state, wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal,

the substance modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal;

another medicament; and

another substance associated with the another medicament in another first release-control state, wherein the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal,

the another substance modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal.

2. The final dosage form ofclaim 1, wherein the substance associated with the medicament in a first release-control state includes:

a particle associated with the medicament in a first release-control state.

3. The final dosage form ofclaim 1, wherein the substance associated with the medicament in a first release-control state includes:

a polymeric material associated with the medicament in a first release-control state.

4. The final dosage form ofclaim 1, wherein the substance associated with the medicament in a first release-control state includes:

a small molecule associated with the medicament in a first release-control state.

5. The final dosage form ofclaim 1, wherein the substance associated with the medicament in a first release-control state includes:

an intelligent molecule associated with the medicament in a first release-control state.

6. The final dosage form ofclaim 1, wherein the substance associated with the medicament in a first release-control state includes:

an encapsulating substance associated with the medicament in a first release-control state.

7. The final dosage form ofclaim 1, wherein the substance associated with the medicament in a first release-control state includes:

a conjugating substance joined with the medicament in a first release-control state.

8. The final dosage form ofclaim 1, wherein the substance associated with the medicament in a first release-control state includes:

a binding substance bound with the medicament in a first release-control state.

9. The final dosage form ofclaim 1, wherein the substance associated with the medicament in a first release-control state includes:

a substance at least one of engaging, or retaining the medicament in a first release-control state.

10. The final dosage form ofclaim 1, wherein the first bioavailability includes a first bioavailability characteristic and the second bioavailability includes a second bioavailability characteristic.

11. The final dosage form ofclaim 1, wherein the first bioavailability to the animal includes the medicament being substantially not bioavailable to the animal.

12. The final dosage form ofclaim 1, wherein the first bioavailability to the animal includes the medicament being substantially bioavailable to the animal.

13. The final dosage form ofclaim 1, wherein the second bioavailability to the animal includes the medicament being substantially not bioavailable to the animal.

14. The final dosage form ofclaim 1, wherein the second bioavailability to the animal includes the medicament being substantially bioavailable to the animal.

15. The final dosage form ofclaim 1, wherein the second bioavailability to the animal includes the medicament being substantially bioavailable to the animal, wherein the second bioavailability to the animal is substantially different than the first bioavailability to the animal.

16. A final dosage form for administering medicament to an animal, the final dosage form comprising:

a medicament;

a substance associated with the medicament in a first state, wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal,

the substance modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second state, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal;

another medicament; and

another substance associated with the another medicament in another first state, wherein the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal,

the another substance modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second state, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal.

17. A method of modifying bioavailability of medicament provided by a final dosage form for administering medicament to an animal, wherein the final dosage form includes

a medicament;

a substance associated with the medicament in a first release-control state, wherein the medicament has a first bioavailability to the animal if the final dosage form is administered to the animal,

the substance modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state, wherein the medicament has a second bioavailability to the animal if the final dosage form is administered to the animal;

another medicament; and

another substance associated with the another medicament in another first release-control state, wherein the another medicament has another first bioavailability to the animal if the final dosage form is administered to the animal,

the another substance modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state, wherein the another medicament has another second bioavailability to the animal if the final dosage form is administered to the animal;

the method comprising:

transforming the final dosage form into a selected medicament release state by initiating an ex vivo exposure of the substance associated with the medicament in a first release-control state or an ex vivo exposure of the another substance associated with the another medicament in another first release-control state to a modification stimulus respectfully selected from the stimulus or the another stimulus.

18. The method ofclaim 17, wherein the transforming the final dosage form into a selected medicament release state by initiating an ex vivo exposure of the substance associated with the medicament in a first release-control state or an ex vivo exposure of the another substance associated with the another medicament in another first release-control state to a modification stimulus respectfully selected from the stimulus or the another stimulus includes:

transforming the final dosage form into a selected medicament release state by initiating an ex vivo exposure of the substance associated with the medicament in a first release-control state and an ex vivo exposure of the another substance associated with the another medicament in another first release-control state to the stimulus and the another stimulus.

19. The method ofclaim 17, further comprising:

receiving a signal indicative of a chosen medicament bioavailability of the final dosage form.

20. The method ofclaim 19, wherein receiving a signal indicative of a chosen medicament bioavailability of the final dosage form includes:

receiving a machine-initiated signal indicative of a chosen medicament bioavailability of the final dosage form.

21. The method ofclaim 19, wherein receiving a signal indicative of a chosen medicament bioavailability of the final dosage form includes:

receiving a human-initiated signal indicative of a chosen medicament bioavailability of the final dosage form.

22. The method ofclaim 17, further comprising:

selecting the medicament-release state of the substance associated with the medicament or of the another substance associated with the another medicament in response to the chosen medicament-bioavailability of the final dosage form.

23. The method ofclaim 22, wherein the selecting the medicament-release state of the substance associated with the medicament or of the another substance associated with the another medicament in response to the chosen medicament-bioavailability of the final dosage form includes:

electronically selecting the medicament-release state of the substance associated with the medicament or of the another substance associated with the another medicament in response to the chosen medicament-bioavailability of the final dosage form, the selecting a medicament-release state based on an electronically-stored database relating medicament-release state and medicament-bioavailability of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state and medicament-bioavailability of the final dosage form.

24. The method ofclaim 17, further comprising:

selecting the modification stimulus from the stimulus or the another stimulus in response to the selected medicament-release state.

25. The method ofclaim 24, wherein the selecting the modification stimulus from the stimulus or the another stimulus in response to the selected medicament-release state includes:

electronically selecting the modification stimulus from the stimulus or the another stimulus in response to the selected medicament-release state, the selecting the modification stimulus based on an electronically-stored database relating stimuli and medicament-release state of the final dosage form, a computer-implemented decision table, a digitally-maintained final dosage form transformation table, or a digital library correlating medicament-release state of the final dosage form and stimuli.

26. An article of manufacture for administering medicament to an animal, the article comprising:

a medicament;

an intelligent molecular means associated with the medicament in a first release-control state, wherein the medicament has a first bioavailability to the animal if the article of manufacture is administered to the animal,

the intelligent molecular means modifiable ex vivo by an exposure to a stimulus to associate with the medicament in a second release-control state, wherein the medicament has a second bioavailability to the animal if the article of manufacture is administered to the animal;

another medicament; and

another intelligent molecular means associated with the another medicament in another first release-control state, wherein the another medicament has another first bioavailability to the animal if the article of manufacture is administered to the animal,

the another intelligent molecular means modifiable ex vivo by an exposure to another stimulus to associate with the another medicament in another second release-control state, wherein the another medicament has another second bioavailability to the animal if the article of manufacture is administered to the animal.

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