US20100256568A1 - Microneedle cartridge assembly and method of applying - Google Patents

Abstract

A microneedle array cartridge includes a web of material having a top face and an opposite bottom face. An adhesive and a microneedle array are disposed on the bottom face of the web of material. A container is disposed relative to the bottom face of the web of material, and has a perimeter portion and a central portion for covering at least part of the microneedle array. At least part of the perimeter portion of the container contacts the adhesive, and the central portion of the container does not contact the adhesive. The perimeter portion and the central portion of the container are integrally formed.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
• The present application claims priority to U.S. Provisional Application Ser. No. 60/694,446, filed on Jun. 27, 2005, which is incorporated herein in its entirety.
FIELD
• The present invention relates to microneedle array cartridges.
BACKGROUND
• Only a limited number of molecules with demonstrated therapeutic value can be transported through the skin via unassisted or passive transdermal drug delivery. The main barrier to transport of molecules through the skin is the stratum corneum (the outermost layer of the skin).
• Devices including arrays of relatively small structures, sometimes referred to as microneedles or micro-pins, have been disclosed for use in connection with the delivery of therapeutic agents and other substances through the skin and other surfaces. The devices are typically pressed against the skin in an effort to pierce the stratum corneum. The microneedle arrays are generally used once and then discarded.
• Microneedles on these devices pierce the stratum corneum upon contact, making a plurality of microscopic slits that serve as passageways through which molecules of active components (e.g., therapeutic agents, vaccines, and other substances) can be delivered into the body. In delivering an active component, the microneedle array can be provided with a reservoir for temporarily retaining an active component in liquid form prior to delivering the active component through the stratum corneum. In some constructions, the microneedles can be hollow to provide a liquid flow path directly from the reservoir and through the microneedles to enable delivery of the therapeutic substance through the skin. In alternate constructions, active component(s) may be coated and dried on the microneedle array and delivered directly through the skin after the stratum corneum has been punctured.
• Transdermal adhesive patches are also available and are generally constructed as an adhesive article with a pressure sensitive adhesive coated onto the surface of a backing comprised of a polymeric film, cloth or the like. Transdermal adhesive patches are provided with an adhesive that allows the patch to be releasably adhered to the surface of the skin where a predetermined dosage of an active component can be put in contact with a small surface area of the skin. An appropriate biocompatible carrier is normally provided to facilitate the absorption of molecules through the stratum corneum over a period of time while the patch remains adhered to the skin.
BRIEF SUMMARY
• Patches, with or without a microneedle array, can have fragile and sanitary characteristics. It is generally desired that the patch and array not be contacted before application to a target site. This presents difficulties in storing and transporting patches to desired locations for eventual application. In addition, providing collars or other protection for microneedle arrays produces bulky structures that require excessive amounts of materials to manufacture and take up large amounts of space during transportation and storage. Moreover, loading a microneedle array on an applicator device can also be time consuming and difficult for operators. Thus, the present invention provides an alternative microneedle cartridge design.
• In a first aspect of the present invention, a microneedle array cartridge includes a web of material having a top face and an opposite bottom face. An adhesive and a microneedle array are disposed on the bottom face of the web of material. A container is disposed relative to the bottom face of the web of material, and has a perimeter portion and a central portion for covering at least part of the microneedle array. At least part of the perimeter portion of the container contacts the adhesive, and the central portion of the container does not contact the adhesive. The perimeter portion and the central portion of the container are integrally formed.
• In another aspect of the present invention, a microneedle array package includes a plurality of adhesive patches separably attached to each other, and each of the adhesive patches carrying a microneedle array.
• In another aspect of the present invention, a microneedle array cartridge includes a web of material having a top face and an opposite bottom face, an adhesive, a microneedle array and a container. The web of material is disposed substantially in a first plane. The adhesive is disposed on the bottom face of the web of material. The microneedle array is disposed relative to the bottom face of the web of material. The container is disposed relative to the bottom face of the web of material, and has a perimeter portion and a central portion for covering at least a portion of the microneedle array. A first region of the perimeter portion is disposed substantially in a second plane that is generally parallel to the first plane, and a second region of the perimeter portion is generally not disposed in the second plane.
• In another aspect of the present invention, a microneedle array cartridge includes a web of material having a top face, an opposite bottom face and defining a perimeter, an adhesive disposed on the bottom face of the web of material, a microneedle array, and a container. The microneedle array is disposed relative to the bottom face of the web of material. The container is disposed relative to the bottom face of the web of material, and has a perimeter portion and a central portion for covering at least a portion of the microneedle array. The perimeter portion of the container generally extends at least to the perimeter of the web of material, and has a pair of opposing cutout regions that do not extend as far as the perimeter of the web of material.
• In another aspect of the present invention, a microneedle array cartridge includes a web of material having a top face, an opposite bottom face and defusing a perimeter, an adhesive disposed on the bottom face of the web of material, a microneedle array, and a container. The microneedle array is disposed relative to the bottom face of the web of material. The container extends only from the bottom face of the web of material, and has a perimeter portion and a central portion for covering at least part of the microneedle array. At least part of the perimeter portion of the container contacts the adhesive and the central portion does not contact the adhesive.
• In another aspect of the present invention, a method for microneedle array application includes slidably mounting a microneedle array cartridge on an applicator device, simultaneously exposing the microneedle array of the cartridge by removing a cover portion of the cartridge when the cartridge is at least partially mounted on the applicator device, and moving the microneedle array toward a target site.
• In another aspect of the present invention, a method of mounting a microneedle array relative to a microneedle array application device includes slidably positioning a microneedle cartridge having a microneedle array and a removable cover at least partially within a retaining portion of the microneedle array application device, rotating the microneedle cartridge relative to the microneedle array application device within the retaining portion of the microneedle array application device in order to break a seal to allow removal of the cover, and exposing the microneedle array of the microneedle cartridge by removing the cover when the microneedle cartridge is at least partially mounted on the microneedle array applicator device.
• The above summary is not intended to describe each disclosed embodiment or every implementation of the present invention. The figures and the detailed description, which follow, more particularly exemplify illustrative embodiments.
BRIEF DESCRIPTION OF DRAWINGS
• FIG. 1 is a perspective view of a first embodiment of a microneedle cartridge.
• FIG. 2 is a cross-sectional view of the microneedle cartridge ofFIG. 1.
• FIG. 3 is a partial cross-sectional view of the microneedle cartridge ofFIGS. 1 and 2 mounted on an applicator device.
• FIG. 4 is a perspective view of the patch ofFIGS. 1,2 and3 mounted on the applicator device ofFIG. 3.
• FIG. 5 is a perspective view of a second embodiment of a microneedle cartridge.
• FIG. 6 is a front cross-sectional view of the microneedle cartridge ofFIG. 5.
• FIG. 7 is a side cross-sectional view of the microneedle cartridge ofFIGS. 6 and 7, rotated 90° relative toFIG. 6.
• FIG. 8 is a bottom view of the microneedle cartridge ofFIGS. 5,6 and7.
• FIG. 9 is a perspective view of a third embodiment of a microneedle cartridge.
• FIG. 10 is a cross-sectional view of the microneedle cartridge ofFIG. 9.
• FIG. 11 is a perspective view of a number of microneedle cartridges arranged as a sheet.
• FIG. 12 is a side view of a number of microneedle cartridges arranged as a roll.
• FIG. 13 is a bottom perspective view of a microneedle cartridge in a mounting fixture.
• FIG. 14 is a bottom perspective view of another embodiment of a microneedle cartridge.
• FIG. 15 is a top perspective view of a mounting fixture and microneedle cartridge partially inserted into an applicator.
• FIG. 16 is bottom perspective view of a mounting fixture and microneedle cartridge partially inserted into an applicator.
• While the above-identified drawing figures set forth several embodiments of the invention, other embodiments are also contemplated, as noted in the discussion. In all cases, this disclosure presents the invention by way of representation and not limitation. It should be understood that numerous other modifications and embodiments can be devised by those skilled in the art, which fall within the scope and spirit of the principles of the invention. The figures may not be drawn to scale. Like reference numbers have been used throughout the figures to denote like parts.
DETAILED DESCRIPTION
• Patches can be used for transdermal delivery of molecules, and can carry microneedle arrays, which have utility for the delivery of large molecules that are ordinarily difficult to deliver by passive transdermal delivery. As used herein, “array” refers to the medical devices described herein that include one or more structures capable of piercing the stratum corneum to facilitate the transdermal delivery of therapeutic agents or the sampling of fluids through or to the skin. “Microstructure,” “microneedle” or “microarray” refers to the specific microscopic structures associated with the array that are capable of piercing the stratum corneum to facilitate the transdermal delivery of therapeutic agents or the sampling of fluids through the skin. By way of example, microstructures can include needle or needle-like structures as well as other structures capable of piercing the stratum corneum. The microneedles are typically less than 500 microns in height, and sometimes less than 300 microns in height. The microneedles are typically more than 20 microns in height, often more than 50 microns in height, and sometimes more than 125 microns in height.
• FIG. 1 is a perspective view of a first embodiment of amicroneedle cartridge20 that includes apatch22 and acontainer24.FIG. 2 is a cross-sectional view of themicroneedle cartridge20. Thepatch22 shown inFIGS. 1 and 2 includes a web ofmaterial26 that forms a backing, and amicroneedle array28 supported by and attached to the web ofmaterial26. The web ofmaterial26 is generally flat, and has anupper face30 and alower face32. The web ofmaterial26 can be comprised of a polymeric film, cloth, nonwoven or the like. An adhesive34, such as a pressure sensitive adhesive, is disposed on thelower face32 of the web ofmaterial26. Themicroneedle array28 is located relative to thelower face32 of the web ofmaterial26 at a generally central portion of the web ofmaterial26, which has a circular shape. Themicroneedle array28 can be attached to the web ofmaterial26, for example, by adhesive, welding, heat bonding, and can be formed integrally with the web ofmaterial26.
• Suitable materials for themicroneedle array28 include those selected from materials such as acrylonitrile-butadiene-styrene (ABS) polymers, polyphenyl sulfides, polycarbonates, polypropylenes, acetals, acrylics, polyetherimides, polybutylene terephthalates, polyethylene terephthalates as well as other known materials and combinations of two or more of the foregoing. Themicroneedle array28 can carry molecules for eventual delivery through the stratum corneum of a patient's skin (i.e., the skin of a human or non-human test subject). Those molecules can be therapeutic agents, vaccines, and other materials. A reservoir can be included with themicroneedle array28 for holding molecules for eventual delivery. Deployment of thepatch22 to a target site permits the molecules to be delivered through or to the stratum corneum.
• The adhesive layer will generally be selected according to the desired end use of the articles prepared by the present method. Examples of suitable adhesives include acrylates, silicones, polyisobutylenes, synthetic rubber, natural rubber, and copolymers and mixtures thereof. Further description of suitable adhesives may be found in U.S. Pat. Nos. 5,656,286 (Miranda et al.), 4,693,776 (Krampe et al.), 5,223,261(Nelson et al.), and 5,380,760 (Wendel et al.) the disclosures of which are incorporated herein by reference.
• Typical examples of flexible films employed as conventional tape backings which may be useful as a backing film include those made from polymer films such as polypropylene; polyethylene, particularly low density polyethylene, linear low density polyethylene, metallocene polyethylenes, and high density polyethylene; polyvinyl chloride; polyester (e.g., polyethylene terephthalate); polyvinylidene chloride; ethylene-vinyl acetate (EVA) copolymer; polyurethane; cellulose acetate; and ethyl cellulose. Coextruded multilayer polymeric films are also suitable, such as described in U.S. Pat. No. 5,783,269 (Heilmann et al.), the disclosure of which is incorporated herein by reference. Layered backings such as polyethylene terephthalate-aluminum-polyethylene composites and polyethylene terephthalate-EVA composites are also suitable. Foam tape backings, such as closed cell polyolefin films used in 3M™ 1777 Foam Tape and 3M™ 1779 Foam Tape are also suitable. Polyethylenes, polyethylene blends, and polypropylenes are preferred polymer films. Polyethylenes and polyethylene blends are most preferred polymer films. In one embodiment, the backing film is translucent or transparent. Additives may also be added to the backing film, such as tackifiers, plasticizers, colorants, and anti-oxidants.
• Thecontainer24 is removably attached to thepatch22 to cover themicroneedle array28. Thecontainer24 includes a circularcentral base portion36, asidewall38 connected at or near the perimeter of thecentral base portion36, and aperimeter lip40 connected to thesidewall38 opposite thecentral base portion36. Afirst portion42 of theperimeter lip40 is adhesively affixed to the adhesive34 on the web ofmaterial26, and asecond portion44 of theperimeter lip40 is spaced from the adhesive34 so as not to adhere to it. This creates a gap or slight separation46 (seeFIG. 2). Thegap46 facilitates separating thecontainer24 from thepatch22 for application of thepatch22 to a patient. However, in one embodiment, a continuous adhesive connection is formed around themicroneedle array28 between the web ofmaterial26 and theperimeter lip40 of thecontainer24. That continuous connection can form a seal. In some instances, the seal may be a hermetic seal, that is, a seal that can prevent entry or escape of air or other vapors, such as moisture vapor. Sealing themicroneedle array28 between the web ofmaterial26 and thecontainer24 helps protect themicroneedle array28 from contamination and damage prior to deployment. In such a configuration the web ofmaterial26 may be considered to be disposed substantially in a first plane and thefirst portion42 of theperimeter lip40 is disposed substantially in a second plane that is generally parallel to the first plane. It should be understood by the term disposed substantially in a plane, that theweb26 andfirst portion42 are largely planar, but that minor variations, for example, due to manufacturing imperfections or due to the flexibility in the web and/or the carrier material may cause slight, but insignificant, deviations from planarity. Thesecond portion44 of theperimeter lip40 is generally not disposed in the second plane.
• As shown, the shape of the container is a cylinder, but it should be understood that other shapes are suitable as long as the base portion is appropriately spaced from themicroneedle array28. For example, thecentral base portion36 andsidewall38 may have the form of a dome, in which case there may be no discernable boundary between thesidewall38 and thecentral base portion36. The sidewalls may be angled and in some embodiments may extend until they contact an opposing sidewall, for example, forming a cone-shaped container. Furthermore, the container may have additional exterior protrusions or indentations to facilitate handling and/or storage. For example, a handling tab may be affixed to the exterior surface of the base portion to make the container more easily graspable.
• Thecentral base portion36 and thesidewall38 of thecontainer24 define a volume in which themicroneedle array28 can rest. Thecontainer24 is spaced from themicroneedle array28, as themicroneedle array28 is generally susceptible to damage from contact during storage, transportation, and at other times prior to deployment. Thecontainer24 can have a relatively low profile, such that thesidewall38 of thecontainer24 preferably has as small a height, H, as possible without damaging or risking damage to themicroneedle array28 through contact. Alow profile container24 reduces space occupied by thecartridge20, for storage and transportation purposes, while still providing protection to themicroneedle array28. Alow profile container24 also reduces the amounts of gases (i.e., air) and contaminants that are exposed to themicroneedle array28 and molecules carried thereon. Because many molecules intended for delivery with themicroneedle array28 can have limited lifespans and may be sensitive to contamination and deterioration, alow profile container24 reduces the volume of air that is exposed to themicroneedle array28 to limit such negative effects. A suitable low-profile height will depend upon the nature of thepatch22 andmicroneedle array28, but the height will typically be less than 2.0 cm, often less than 1.5 cm, and sometimes less than 1.0 cm.
• Thecontainer24 can be formed of a polymer material. Generally, a rigid material is selected in order to better protect themicroneedle array28 from damage and to facilitate storage (e.g., for stacking a plurality of microneedle cartridges20). In one embodiment, thecontainer24 is a transparent or translucent material. In one embodiment, thecontainer24 is opaque to protect themicroneedle array28 from exposure to light.
• FIG. 3 is a partial cross-sectional view of themicroneedle cartridge20 held on anapplicator device50. As shown inFIG. 3, theapplicator device50 has a skin-contactingface52, arecess54, a substantiallycircular opening56 defined in abottom portion58 of therecess54, and a pair ofretainer members60 that each have substantially flat upper surfaces62. Theretainer members60 are generally elongate and their substantially flatupper surfaces62 are generally parallel to and facing thebottom portion58 of therecess54. The pair ofretainer members60 are located at opposite portions of theopening56 and are connected at one side of therecess54. Theretainer members60 define an opening at one end for accepting patches between theretainer members60 and thebottom portion58 of therecess54. The upper surfaces62 of theretainer members60 may be non-stick or release surfaces. A non-stick or release surface can be achieved, for example, by a non-stick or release coating applied to the upper surfaces62. The non-stick or release coating can be selected according to the desired use of theapplicator device50. For instance, a release coating, such as a low surface energy silicone, fluoropolymer, or fluoro-silicone release coating, can be selected based upon the adhesives used with patches applied using thepatch application device50
• As shown inFIG. 3, thepatch22 is disposed between theretainer members60 and thebottom portion58 of therecess54. Themicroneedle array28 carried by thepatch22 faces away from opening56 in theapplicator device50. Thepatch22 contacts theupper surfaces62 of theretainer members60, but generally does not adhere firmly to theretainer members60 due to the non-stick or release character of the upper surfaces62.
• FIG. 4 is a perspective view of thepatch22 mounted on theapplicator device50. In a fully mounted position, as shown inFIG. 4, thepatch22 is generally aligned relative to theopening56 in the applicator device50 (theopening56 is not visible inFIG. 4). Theretainer members60 havecutaway portions64 that provide an enlarged, partially circular open region that is generally aligned with theopening56 on thebottom portion58 of therecess54. The open region defined by thecutaway portions64 facilitates patch application by reducing the amount of deflection of thepatch22 required to move thepatch22 from a mounted position on theapplicator device50 to a target location, during deployment. Further details of applicators suitable for use with microneedle array cartridges of the present invention may be found in U.S. Patent Application Ser. No. 60/694,447 (Attorney Docket No. 60874US002) filed on Jun. 27, 2005, the disclosure of which is hereby incorporated by reference.
• Themicroneedle cartridge20 allows for simple and easy mounting of thepatch22 to theapplicator device50, for eventually applying the microneedle array28 (thearray28 is not visible inFIG. 4) to a target site. Mounting themicroneedle patch22 on theapplicator device50 includes the following steps. First, themicroneedle cartridge20, with thecontainer24 affixed thereto, is partially slid onto theretainer members60. Ends of theretainer members60 are positioned in thegap46 formed between the web ofmaterial26 and theperimeter lip40 of thecontainer24 of themicroneedle cartridge20. Then themicroneedle cartridge20 is slid further along theretainer members60, simultaneously separating thecontainer24 from the web ofmaterial26, until thepatch22 is fully mounted on the applicator device50 (e.g., such that themicroneedle array28 is aligned with theopening56 defined in thebottom portion58 of the recess54). Thecontainer24 is removed from (i.e., separated from) thepatch22 to uncover and expose themicroneedle array28 prior to microneedle deployment. An operator may need to pull thecontainer24 away from the applicator device50 (e.g., by applying a force perpendicular to the skin-contactingface52 of the applicator device50) in order to fully separate thecontainer24 from thepatch22, during the process of mounting or once mounted onto an applicator device. The motion between themicroneedle cartridge20 and theapplicator device50 is a relative motion which may be accomplished by moving one or both of theapplicator device50 and themicroneedle cartridge20. In one embodiment, a mountingfixture100 may be used to assist in mounting thepatch22 of themicroneedle cartridge20 to theapplicator device50. A perspective view of the bottom of a mountingfixture100 is shown inFIG. 13. The mountingfixture100 comprisesalignment members110 andcartridge holder members120. The cartridge20 (shown in more detail inFIG. 14) includes apatch22 and acontainer24. Thepatch22 includes a web ofmaterial26 that forms a backing, and a microneedle array28 (not shown) supported by and attached to the web ofmaterial26. An adhesive34, such as a pressure sensitive adhesive, is disposed on thelower face32 of the web ofmaterial26. Thecontainer24 is removably attached to thepatch22 to cover themicroneedle array28. Thecontainer24 includes an asymmetriccentral base portion36, asidewall38 connected at or near the perimeter of thecentral base portion36, and aperimeter lip40 connected to thesidewall38 opposite thecentral base portion36. Asecond portion44 of theperimeter lip40 is spaced from the adhesive34 so as not to adhere to it. This creates a gap orslight separation46. Thegap46 facilitates separating thecontainer24 from thepatch22 for application of thepatch22 to a patient. The asymmetric shape of thecentral base portion36 may be selected so as to mate with the opening provided by thecartridge holder members120 in an orientation that presents thegap46 to the front of the mountingfixture100. This prevents the user from accidentally misaligning thegap46 with respect to theapplicator device50.
• The mountingfixture100 with mountedcartridge20 is shown partially mated with anapplicator device50 inFIGS. 15 and 16. The alignment guides110 contact anouter recess55, thus providing for alignment of thecartridge20 with theretainer members60 of theapplicator50. The mounting fixture may be used to fully insert thecartridge20 into theapplicator50, at which time the mountingfixture100 andcontainer24 may be removed, thereby leaving thepatch22 mounted in theapplicator50. In one embodiment, the mounting fixture may be easily grasped by a user or otherwise fixed in space, so that the user may bring theapplicator50 towards the stationary mounting fixture to load thepatch22 into theapplicator50. For example, the mountingfixture100 may be part of a base station that holdsmultiple cartridges20 and advances them to thecartridge holder members120 one at a time. In another embodiment, the mountingfixture100 may be integrated with packaging material used to hold one ormore cartridges20. For example, a box of cartridges may have a mounting fixture affixed to an outside surface so that a user could remove a cartridge from the box, place the cartridge in the mounting fixture, and load the cartridge into the applicator as described above. In still another embodiment, a tray holding multiple cartridges could be provided, wherein each cartridge is held in a mounting fixture integrally molded into the tray. Thus each cartridge could be directly loaded from the tray into an applicator.
• The mounting configuration shown inFIGS. 3 and 4 is provided by way of example, and not limitation. In further embodiments, other means of mounting a patch on the applicator device can be used. For instance, in further embodiments, one or more patches can be stored inside theapplicator device50 prior to application, and then dispensed for application to a target site.
• FIGS. 5-8 show a second embodiment of amicroneedle cartridge70.FIG. 5 is a perspective view of themicroneedle cartridge70.FIG. 6 is a front cross-sectional view of themicroneedle cartridge70, andFIG. 7 is a side cross-sectional view of themicroneedle cartridge70.FIG. 8 is a bottom view of themicroneedle cartridge70.
• Themicroneedle cartridge70 includes apatch22 and acontainer24. Thepatch22 includes a web ofmaterial26, amicroneedle array28 and an adhesive34 on abottom face32 of the web ofmaterial26, and is generally similar to that shown and described with respect toFIGS. 1-4 above. Thecontainer24 is removably attached to thepatch22 to cover themicroneedle array28. Thecontainer24 includes a circularcentral base portion36, asidewall38 connected at or near the perimeter of thecentral base portion36, and aperimeter lip40 connected to thesidewall38 opposite thecentral base portion36. A pair ofopposed cutouts72 are provided in theperimeter lip40. Thecutouts72 in theperimeter lip40 make thecontainer24 smaller than a width or diameter of thepatch22 in particular regions, and expose portions of the adhesive34 on thebottom face32 of the web ofmaterial26.
• A pair ofstiffeners74 are provided on anupper face30 of the web ofmaterial26. Thestiffeners74 provide additional rigidity to thepatch22 in order to reduce flexing, bending and other undesired deformation of themicroneedle array28 prior to and during handling and deployment. In particular, thestiffeners74 will reduce flexing in the area of thepatch22 that is suspended above thecentral base portion36. As shown inFIGS. 6-8, thestiffeners74 are parallel to each other and generally aligned relative to thesidewall38 of thecontainer24. In further embodiments, more orfewer stiffeners74 can be provided. Furthermore, thestiffeners74 can be provided at different locations on thepatch22 than those shown inFIGS. 6-8. It should be understood that thestiffeners74 are optional and that in certain embodiments thepatch22 may have sufficient resistance to bending or flexing without the need foradditional stiffeners74. For example, themicroneedle array28 may extend near or up to the inner surface of thesidewalls38 and thereby provide sufficient rigidity in the suspended portion of thepatch22.
• FIG. 9 is a perspective view of a third embodiment of amicroneedle cartridge80.FIG. 10 is a cross-sectional view of themicroneedle cartridge80. As shown inFIGS. 9 and 10, themicroneedle cartridge80 includes apatch22 and acontainer24. Thepatch22 includes a web ofmaterial26, amicroneedle array28 and an adhesive34 on abottom face32 of the web ofmaterial26, and is generally similar to those shown and described with respect toFIGS. 1-8 above. The container is removably attached to thepatch22 to cover themicroneedle array28. Thecontainer24 includes a circularcentral base portion36, asidewall38 connected at or near the perimeter of thecentral base portion36, and aperimeter lip40 connected to thesidewall38 opposite thecentral base portion36. Agasket82 is disposed to adhere to thelip40 of thecontainer24 and patch (i.e., to the web ofmaterial26 or the adhesive34). Thegasket82 is disposed in a substantially continuous band around themicroneedle array28 in order to form a seal between thepatch22 and thecontainer24. In one embodiment, thegasket82 is an adhesive. In one embodiment a different adhesive may be used for the gasket than that used for the adhesive34 adhered to thebottom face32 of the web ofmaterial26.
• Inserting thecartridge80 into an applicator device can be generally similar to that described above with respect toFIGS. 1-8. Additionally, the seal formed by thegasket82 can be broken during an inserting procedure. For example, an operator can rotate thecartridge80 relative to an applicator device to slice or otherwise break the seal using a blade or other means disposed on the applicator device.
• A plurality of individual microneedle cartridges can be arranged as a package for providing advantages in storage, transportation and dispensing them.FIG. 11 is a perspective view of a number ofmicroneedle cartridges90 arranged as asheet92. Thesheet92 includes aliner94 on which thecartridges90 are carried. Theindividual cartridges90 can be removably adhered to theliner94, or secured together by other methods. In some embodiments,perforations96 can be provided in theliner94 for separatingindividual cartridges90.
• FIG. 12 is a side view of a number ofmicroneedle cartridges90 arranged as aroll98. Theroll98 includes aliner94 on which thecartridges90 are carried and acore99 around which theliner94 is wound. Theindividual cartridges90 can be removably adhered to theliner94, or secured together by other methods. In some embodiments,perforations96 can be provided in theliner94 for separatingindividual cartridges90.
• The packages shown and described with respect toFIGS. 11 and 12 permit storage of a plurality of cartridges in close proximity to each other. Individual cartridges can be separated from the others as desired for use. Those packages can also help reduce time between microneedle array deployments, by facilitating “reloading” of applicator devices between array deployments.
• Applicators used to apply a microneedle array or patch will typically accelerate the microneedle device to reach a desired velocity that is effective to pierce the microneedles into the skin. The desired velocity is preferably controlled to limit or prevent stimulation of the underlying nerve tissue. The maximum velocity achieved by the microneedle array upon impact with the skin is often 20 meters per second (m/s) or less, potentially 15 m/s or less, and possibly 10 m/s or less. In some instances, the maximum velocity be 8 m/s or less. In other instances, the minimum velocity achieved by the microneedle array upon impact with the skin is often 2 m/s or more, potentially 4 m/s or more, and possibly 6 m/s or more.
• The microneedle arrays useful in the various embodiments of the invention may comprise any of a variety of configurations, such as those described in the following patents and patent applications, the disclosures of which are herein incorporated by reference. One embodiment for the microneedle arrays comprises the structures disclosed in U.S. Patent Application Publication No. 2003/0045837. The disclosed microstructures in the aforementioned patent application are in the form of microneedles having tapered structures that include at least one channel formed in the outside surface of each microneedle. The microneedles may have bases that are elongated in one direction. The channels in microneedles with elongated bases may extend from one of the ends of the elongated bases towards the tips of the microneedles. The channels formed along the sides of the microneedles may optionally be terminated short of the tips of the microneedles. The microneedle arrays may also include conduit structures formed on the surface of the substrate on which the microneedle array is located. The channels in the microneedles may be in fluid communication with the conduit structures. Another embodiment for the microneedle arrays comprises the structures disclosed in U.S. Patent Application Publication No. 2005/0261631, which describes microneedles having a truncated tapered shape and a controlled aspect ratio. Still another embodiment for the microneedle arrays comprises the structures disclosed in U.S. Pat. No. 6,091,975 (Daddona, et al.) which describes blade-like microprotrusions for piercing the skin. Still another embodiment for the microneedle devices comprises the structures disclosed in U.S. Pat. No. 6,313,612 (Sherman, et al.) which describes tapered structures having a hollow central channel. Still another embodiment for the micro arrays comprises the structures disclosed in U.S. Pat. No. 6,379,324 (Gartstein, et al.) which describes hollow microneedles having at least one longitudinal blade at the top surface of tip of the microneedle.
• Microneedle patches of the present invention may be used to deliver drugs (including any pharmacological agent or agents) through the skin in a variation on transdermal delivery, or to the skin for intradermal or topical treatment, such as vaccination.
• In one aspect, drugs that are of a large molecular weight may be delivered transdermally. Increasing molecular weight of a drug typically causes a decrease in unassisted transdermal delivery. Microneedle arrays of the present invention have utility for the delivery of large molecules that are ordinarily difficult to deliver by passive transdermal delivery. Examples of such large molecules include proteins, peptides, nucleotide sequences, monoclonal antibodies, DNA vaccines, polysaccharides, such as heparin, and antibiotics, such as ceftriaxone.
• In another aspect, microneedle patches of the present invention may have utility for enhancing or allowing transdermal delivery of small molecules that are otherwise difficult or impossible to deliver by passive transdermal delivery. Examples of such molecules include salt forms; ionic molecules, such as bisphosphonates, preferably sodium alendronate or pamedronate; and molecules with physicochemical properties that are not conducive to passive transdermal delivery.
• In another aspect, microneedle patches of the present invention may have utility for enhancing delivery of molecules to the skin, such as in dermatological treatments, vaccine delivery, or in enhancing immune response of vaccine adjuvants.
• Microneedle patches may be used for immediate delivery, that is where they are applied and immediately removed from the application site, or they may be left in place for an extended time, which may range from a few minutes to as long as 1 week. In one aspect, an extended time of delivery may be from 1 to 30 minutes to allow for more complete delivery of a drug than can be obtained upon application and immediate removal. In another aspect, an extended time of delivery may be from 4 hours to 1 week to provide for a sustained release of drug.
• Although the present invention has been described with reference to several alternative embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention. For instance, various types of microneedle arrays can be utilized according to the present invention, as well as various types of microneedle applicator devices.

Claims (40)

1. A microneedle array cartridge comprising:

a web of material having a top face and an opposite bottom face;

an adhesive disposed on the bottom face of the web of material;

a microneedle array disposed relative to the bottom face of the web of material; and

a container disposed relative to the bottom face of the web of material having a perimeter portion and a central portion for covering at least part of the microneedle array, wherein at least part of the perimeter portion contacts the adhesive and the central portion does not contact the adhesive, and wherein the perimeter portion and the central portion are integrally formed.

2. The microneedle array cartridge ofclaim 1, wherein a first region of the perimeter portion contacts the adhesive.

3. The microneedle array cartridge ofclaim 2, wherein a second region of the perimeter portion does not contact the adhesive.

4. The microneedle array cartridge ofclaim 1, and further comprising at least one stiffener disposed along the web of material.

5. The microneedle array cartridge ofclaim 4, wherein a pair of stiffeners are provided.

6. The microneedle array cartridge ofclaim 4, wherein the at least one stiffener has an elongate shape.

7. The microneedle array cartridge ofclaim 4, wherein the at least one stiffener has a length at least as long as a width or diameter of the central portion of the container.

8. The microneedle array cartridge ofclaim 1, wherein the web of material defines a web perimeter, and wherein at least a portion of the perimeter portion of the container generally extends at least to the web perimeter.

9. The microneedle array cartridge ofclaim 1, wherein the perimeter portion of the container defines a pair of cutout regions where the perimeter portion does not extend as far as the web perimeter.

10. The microneedle array cartridge ofclaim 1, wherein a seal is formed between the web of material and the perimeter portion of the container.

11. The microneedle array cartridge ofclaim 10, and further comprising a gasket disposed between the web of material and the perimeter portion of the container for forming the seal.

12. The microneedle array cartridge ofclaim 10, and further comprising a heat seal between the web of material and the perimeter portion of the container for forming the seal.

13. The microneedle array cartridge ofclaim 12, wherein the seal is hermetic.

14. The microneedle array cartridge ofclaim 1, wherein the central portion of the container has a base and at least one sidewall, and wherein the at least one sidewall has a low profile relative to the microneedle array.

15. The microneedle array cartridge ofclaim 14, wherein the base of the central portion of the cartridge is spaced from the microneedle array.

16. The microneedle array cartridge ofclaim 1, wherein the array and web of material are integrally formed.

17. A microneedle array package comprising:

a plurality of adhesive patches separably attached to each other, each of the adhesive patches carrying a microneedle array.

18. The microneedle array package ofclaim 17, wherein the package is in the form of a roll.

19. The microneedle array package ofclaim 17, wherein the package is in the form of a sheet.

20. A microneedle array cartridge comprising:

a web of material disposed substantially in a first plane, the web of material having a top face and an opposite bottom face;

an adhesive disposed on the bottom face of the web of material;

a microneedle array disposed relative to the bottom face of the web of material; and

a container disposed relative to the bottom face of the web of material having a perimeter portion and a central portion for covering at least part of the microneedle array, wherein a first region of the perimeter portion is disposed substantially in a second plane that is generally parallel to the first plane, and wherein a second region of the perimeter portion is generally not disposed in the second plane.

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