FIELD OF THE INVENTIONThis invention relates to oral administration forms and to processes for their preparation.[0001]
BACKGROUND OF THE INVENTIONGasified particles are known in the art as particles that comprise a core material, which encapsulates a pressurized gas that escapes as the core material dissolves or shatters.[0002]
Processes for making gasified particles are known in the art of candy making. For example, processes for making gasified confections are described in the following publications: U.S. Pat. Nos. 3,985,909, 3,985,910 and 4,001,457.[0003]
U.S. Pat. No. 4,289,794 describes a method for preparing gasified candy whereby a sugar melt is gasified at superatmospheric pressure and then is cooled below its fusion temperature under superatmospheric pressure to form a gasified candy. As the gasified candy is wetted in the mouth the candy melts and the gas escapes producing an entertaining popping sensation.[0004]
WO 99/64555 describes laundry detergent products that include gasified particles, and may also include other materials such as bleaching agents and conventional detergent composition adjuvants. The gasified particles that are used in the laundry detergent are said to increase the rate of product dissolution in the wash water and add desirable product aesthetics in the form of colored speckles. In addition, the gasified particles can provide both audible and olfactory signals to the consumer that the product is working.[0005]
Another use of gasified particles is described in U.S. Pat. No. 6,310,014 wherein a composition comprising a gasified solid and an anhydrous liquid base is described. Such composition is said to be useful for personal and household care and to deliver an audible cracking or popping sound during use.[0006]
Gasified particles are also known for use in cosmetic treatments, particularly hair treatments as described in EP 1059076. The cosmetic compositions contain gasified particles and the gas is released on contact with water or moisture.[0007]
Effervescent pharmaceutical compositions for oral administration are also known in the art. An effervescent pharmaceutical composition includes compounds which evolve gas by means of a chemical reaction which takes place upon exposure of the effervescent pharmaceutical composition to water or other fluids.[0008]
Pharmaceutical compositions comprising an effervescent agent are described for example, in U.S. Pat. Nos. 6,350,470 and 5,178,878 and in EP 1082106.[0009]
SUMMARY OF THE INVENTIONThe present invention provides, according to the first aspect thereof, an oral administration form comprising an active ingredient and a pressurized gas, said pressurized gas being trapped in cavities within a pharmaceutically acceptable material, in a manner that allows its escape upon dissolution or shattering of the administration form. The active ingredient may be included in the material trapping the pressurized gas in the cavities thereof. An administration form according to the invention may comprise more than one active ingredient, and it preferably comprises a pharmaceutically acceptable carrier.[0010]
The term “pressurized gas” refers to a gas at a pressure more than 1 atmosphere.[0011]
The oral administration form of the present invention may further comprise coloring, flavoring and other pharmaceutical or neutraceutical excipients.[0012]
It should be noted that the term “administration form” should be construed in a broad sense and includes any form administered for the purpose of achieving a therapeutic effect in humans or animals. It may be sold as a pharmaceutical administration form carrying a label as to the intended indication, whether as a prescription drug or over the counter, or it may be sold without any specific indication, for example as a neutraceutical (neutraceuticals are often referred to as “food additives” or “food supplements”).[0013]
“An oral administration form” is an administration form, the swallowing of which is permissible. Such an administration form is usually intended to be given through the mouth, for swallowing, for treating the mouth cavity, etc.[0014]
The term “active ingredient” should be construed in a broad sense as including any ingredient considered to have a therapeutic effect when delivered to a subject in need thereof. The active ingredient may be an analgesic, an antipyretic agent, an anti-inflammatory agent, a vitamin, an expectorant, an antibiotic, an anti-hypertensive, etc. Thus, it may be a drug such as paracetamol, diphenhydramine, dextromethorphan, lidocaine, loratadine, ibuprofen, pseudoephedrine, enalapril, calcium carbonate, etc, a vitamin or mineral such as vitamin C, vitamin E, biotin, selenium, zinc, etc, a food additive such as echinacea, propolis, soy extract, etc. or a veterinary active ingredient such as nitroscanate, abamectin, ivermectin, etc. The active ingredient may be taste masked, for instance by coating or microencapsulation.[0015]
Non limiting examples of suitable materials for trapping therein the gas are sugars such as glucose, fructose, sucrose, lactose, maltose, corn syrup and mixtures thereof.[0016]
The gas trapped in the cavities may be any pharmaceutically acceptable inert gas. The term “inert” indicates that the gas does not react with the pharmaceutically acceptable material, in the cavities of which the pressurized gas is trapped and the other ingredients included in the administration form during preparation, storage or use. Non limiting examples of gases suitable for the preparation of the oral administration form are carbon dioxide, nitrogen, air, helium, argon, and neon.[0017]
An oral administration form according to the present invention may have benefits in many circumstances, for instance, it may be popular with children that will like the popping sensation and will be more willing to take a popping administration form than one that does not create a popping sensation. The escape of the gas does not only produce a pleasant sensation but may also stimulate saliva production, thereby providing additional saliva to aid dissolution in the mouth. Similarly, it may be used to enhance dissolution of tablets or powders in a drinking liquid. Such tablets may be useful for the elderly or swallow-problem population. It may be used in semi-solids, oils, suspensions or solid preparations to enhance disintegration or dissolution of the active ingredients either in the mouth or in the stomach or intestine.[0018]
Particles which contain trapped pressurized gas may be coated by any suitable material that would protect them from direct contact with water or moisture during storage. However, such a coating material should dissolve when the escape of the gas is required. Suitable coating materials may be for instance, cocoa butter that melts in the mouth, biodegradable polymers typically used for gastrointestinal delivery of drugs (such as enteric polymer that dissolves in the intestine), etc.[0019]
The oral administration form according to the present invention may have different forms, such as a tablet, powder, pellets, capsule, syrup, oil, suspension, gel, drops and various candy-like forms.[0020]
In one non-limiting example, candy-like administration form may be a chocolate bar including gasified particles and an active ingredient.[0021]
The present invention further provides a method for preparing a gasified oral administration form according to the present invention, the method comprising:[0022]
i) preparing a mixture comprising an active ingredient, and a pharmaceutically acceptable material trapping pressurized gas within cavities thereof; and[0023]
ii) processing the mixture to obtain an administration form, said processing being under conditions that permits said gas to escape upon dissolution or shattering of the administration form.[0024]
The mixture mentioned in (i) above may comprise more than one active ingredient.[0025]
The present invention further provides a method for preparing a gasified oral administration form comprising:[0026]
i) melting a pharmaceutically acceptable material to obtain a melt;[0027]
ii) adding a gas and at least one active ingredient and optionally a pharmaceutically acceptable excipient into the melt under superatmospheric pressure to obtain a liquid pharmaceutical composition;[0028]
iii) casting the liquid pharmaceutical composition into a mold under superatmospheric pressure;[0029]
iv) solidifying the cast pharmaceutical composition under conditions suitable to obtain a gasified oral administration form; and releasing the pressure.[0030]
The solidification mentioned above in (iv) may be done in a mold having the form of a desired administration form, for instance, a tablet.[0031]
Alternatively, the gasified pharmaceutical composition obtained by the above method in (iii) may be processed to an oral administration form according to the present invention by the following steps:[0032]
(iv) solidifying said gasified pharmaceutical composition to obtain a solid gasified pharmaceutical composition;[0033]
(v) grinding the solid gasified pharmaceutical composition to obtain a popping powder;[0034]
(vi) optionally adding excipients to said powder and mixing them together; and[0035]
(vii) processing the obtained powder or mixture to obtain an oral administration form which produces popping sensation when it is wetted.[0036]
The active ingredient used in any of the above methods may be coated or microencapsulated with a taste-masking material, enteric polymers, humidity protective materials, oxidation protective materials etc.[0037]
According to an additional aspect of the invention there is provided a method for orally administering an active ingredient to a patient. The method comprising orally administering to the subject an oral administration form according to the present invention. This method may be used for oral administration of drugs to subjects reluctant to take pharmaceutical compositions that do not create a popping sensation upon wetting.[0038]
Further provided by the invention is a method for treating a patient by orally administering to him an administration form according to the present invention.[0039]
DETAILED DESCRIPTION OF THE INVENTIONIn order to understand the invention and to see how it may be carried out in practice, several specific embodiments will now be described, by way of non-limiting examples only.[0040]