MXPA96006041A - Dosage form of rapida disoluc - Google Patents

Abstract

A fast-dissolving, unbreakable flavor masking composition that provides immediate release of pharmaceutically acceptable active ingredients.

Description

METHOD OF DOSAGE OF QUICK DISSOLUTION TECHNICAL FIELD The present invention relates to taste masking compositions, of rapid dissolution. unbreakable of good taste, which provide immediate release of pharmaceutically acceptable active ingredients. r- BACKGROUND OF THE INVENTION A topic in which many doctors and pharmacists are deeply interested refers to the notion of patient compliance. Interest is focused on how to maintain or increase compliance with prescribed regimens. A major obstacle with respect to medication compliance refers to the patient's inability or inability to swallow traditional solid dosage forms. Recognizing the problem, manufacturers strive to introduce novel formulations that will revolutionize the technology of solid dosage forms and meet this common need. An approach has focused on taste masking technology. Flavor masking of pharmaceutically active ingredients is easily accomplished by creating structural matrices with, or covering, such **, "oducts with different types of" taste masking agents. "Examples of the prior art include polymeric polycarboxylates (US Pat. 4,971,791), clay silicates (US Patent No. 3,140,978) and polysaccharide or natural gums (US Patent No. 5,288,500) Another approach followed by a number of pharmaceutical manufacturers to improve patient compliance concerns the use of technologies "Rapidly dissolving." Various methods for carrying out this form of technology have been described, for example, in U.S. Patent No. 4,642,903, U.S. Patent No. 4,946,684, U.S. Patent No. 4,305,502, U.S. Patent No. 4,371,516, U.S. Pat. No. 5,188,825, U.S. Patent No. 5,215,756 and U.S. Patent No. ,298,261. The use of effervescent compositions is a means. particularly well known to achieve rapid dissolution of the vehicle. The effervescent compositions are prepared by mixing active ingredients together with an appropriate effervescent system. The effervescent system usually comprises an acidifying agent and a carbonate-containing material which, by the addition of an aqueous liquid, dissolves into a vigorous effervescence. The effervescent technology is further described in chapter 6 of "Pharmaceutical Dosage Forms: Tablets", Vol. I, 2a. ed. A lieberrnan ed., 1989, Riarcel Dekker, Inc., which is incorporated herein by reference.

Examples of such effervescent compositions include U.S. Patent No. 3,882,228 to Boncey et al., which describes the preparation of wettable aspirin particles.The aspirin particles are coated in a spray-drying process with a mixture of a water-soluble coating material, a wetting agent, and / or a water-soluble film-forming agent The coated aspirin particles are then incorporated into the effervescent tablets, see also US Patent No. 4,687,662 to Schobel, which describes a effervescent composition of rapid therapeutic dissolution The composition is prepared by mixing a granulated therapeutic agent, having a predetermined particle size, with an effervescent system having approximately the same particle size.Efersive compositions that provide a controlled release include the Patent North American No.

No. 4,940,588 to Sparks et al., Which discloses a controlled release powder comprising discrete microparticles ("pharamams") composed of a pharmacologically active ingredient and at least one non-toxic polymer in the form of a multi-matrix, and also US Patent No. 5, 055,306 to Barry et al., Which describes an effervescent sustained release composition. The composition of Barry and others is prepared by compressing granules coated with a water-swellable acrylic polymer, .Insoluble in water and? n derivative of hydroxylated elulose soluble in water together with an effervescent system to form effervescent tablets. Both Sparks and others, and Barry and others, describe their compositions as resistant to breaking (ie, unbreakable). U.S. Patent No. 5,178,878 to Uehling et al. Describes effervescent dosage forms comprising microparticles. The composition is composed of microparticles substantially comprised in, or in the alternative, formed in a matrix with a protective polymer. The polymeric substances of the invention are added to increase the taste masking properties of the effervescent system. The microparticles are described as "breakable" as opposed to the "unbreakable" particles of Sparks and others, and Barry and others. Although the prior art discloses different compositions useful in taste masking and facilitation of the dissolution of vehicles containing pharmacologically active compounds, there is still a need for improved pharmaceutical compositions of masked taste, immediate release and rapid dissolution. The prior art disclosures in this field, which relate to immediate release compositions, have not directed their attention to form an unbreakable matrix between the taste masking agent and the pharmaceutically active compounds. The incorporation of such a matrix provides reliable taste masking since it is not easily Ornpe (by chewing) to release the bitter taste active ingredients from the matrix. In addition, the pharmaceutical compositions maintain their immediate release profile. Therefore, it is an object of the present invention to provide a taste-free immediate release composition. It is a further object of the present invention to provide an unbreakable rapid dissolution composition, which incorporates pharmaceutical active ingredient. Another additional object is to provide a method of manufacturing a fast-dissolving, good-tasting drug containing active pharmaceutical ingredients. These additional objectives and objectives will become readily apparent from the detailed description that follows.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to an oral pharmaceutical composition comprising: (a) An unbreakable drug matrix comprising: i) a taste masking agent; and ii) an effective and safe amount of a pharmaceutically active ingredient; and (b) an orally acceptable pharmaceutical carrier wherein said pharmaceutically acceptable carrier rapidly disintegrates in aqueous solution without the need for a drug and wherein said composition provides for an immediate release of the pharmaceutically active ingredient. The present invention also relates to methods of treating symptoms of respiratory diseases, such as those associated with cough, cold, flu, allergy and cold symptoms as well as gastrointestinal disorders; comprising the administration of an effective and safe amount of the compositions of the present invention. All percentages and proportions herein are by weight unless otherwise specified. Additionally, all measurements are made at 25 ° C unless otherwise specified. The term "effective and safe amount", as used herein, is an amount that is effective in mitigating and / or treating the symptoms for which the active ingredient in a human is indicated without undue adverse side effects, in proportion with a reasonable risk / benefit ratio. The term "unbreakable", as used herein, means the ability to withstand the forces commonly associated with the chewing process (i.e. direct compression forces ranging from about 4 to 5.6 kilograms). The term "immediate release" as used herein, means that at least 75% of said ingredient < «Pharmacist is released within 45 minutes after administration. The term "rapidly deepen rabies" means that the particles formed disintegrate in water within 30 seconds, preferably, the formed particle disintegrates (dissolves or disperses) in 10 seconds or less. Methods for the measurement of disintegration time are described in US Patent No. 4,371,516 to Gregory et al., Which is incorporated herein by reference.

DETAILED DESCRIPTION OF THE INVENTION The compositions of the present invention contain essential components as well as different non-essential components as indicated below.

ESSENTIAL COMPONENTS Flavor Enrichment Agent The first essential component of the present invention is a safe and effective amount of a taste masking agent. Flavor masking agents suitable for the present invention include those substances effective to mask the unfavorable taste or flavors of edible compounds and which will form an unbreakable matrix when combined with an active ingredient Strynaceutical. The taste masking agent can be substantially incorporated into the pharmaceutically active ingredient. The term "substantially incorporated" as used herein means that the taste masking agent substantially shields the pharmaceutically active ingredient from contact with the medium outside the active ingredient. Alternatively and / or additionally, the pharmaceutically active ingredient can be dispersed or dissolved within the taste masking agent to form the drug matrix compositions. Suitable taste masking agents are described below. Silicate clays are useful taste masking agents. Examples of such clays including the use of magnesium trisilicate are described in US Patent No. 3,085,942 to Clifton et al., April 16, 1963; and U.S. Patent 4,581,232 of April 8, 1966; 4,632,821 of December 30, 1986; 4,462,231 of February 10, 1987; 4,643,898 of 17 February 1987; 4,643,892 of February 17, 1987; 4,647,449 of March 3, 1987; 4,647,450 of March 3, 1987; 4,647,459 of March 3, 1987; 4,649,041 of March 19, 1987; 4,650,663 of March 17, 1987 for Peter and others, all of which are incorporated herein by reference. Additional examples using aluminum magnesium silicates are described in U.S. Patent No. 4,761,274 on August 2, 1988, to Denick, Jr. and others; Urtearnencana Patent No. 4,753,800 of June 28, 1988, for Mozda, and US Patent No. 3,140,978, July 14, 1964, by Zentner; all of which are incorporated herein by reference. Additionally, acrylic polymer reams are useful taste masking agents and suitable for use in the present invention. The use of acrylic polymer resins in this character has been described, for example, in U.S. Patent No. 4,940,588, U.S. Patent No. 4,971,791; U.S. Patent No. 5,055,306 and U.S. Patent No. 5,178,878, and are incorporated herein by reference. Natural gums such as Karaya gum, gum arabic, and tragacanth gum and polysaccharide gums such as xanthine gum can also be used as the taste masking agent of the present invention. Gums useful for the present invention are also described in the U.S. Patent No. 5,288,500 incorporated herein by reference. Waxes suitable for use as flavor masking agents in the present invention include mono- or di-glyceride, carnauba wax, and paraffin wax. A particularly useful example of such taste masking waxes appears in the encapsulated "microsponge" technology, marketed by Partióle Dynamics under the trademark Descote®.

Active pharmaceutically acceptable agents. The pharmaceutically acceptable active ingredients useful in the present invention can be selected from different groups of chemical compounds or materials suitable for oral administration and having a pharmacological action. These compounds or pharmaceutically acceptable active materials must be compatible with the other essential and compatible ingredients in combination with other active materials or compounds included. The compueetoe or pharmaceutically acceptable active materials are present at a level of from about 0.01 to 90%, preferably from 0.1 to 75%, preferably from 1.0 to 50% and most preferably from about 1.0 to 25%. Pharmaceutically acceptable active materials or compounds may include, but are not limited to: bronchodilators, anorexics, antihytaryninics, nutritional supplements (such as vitamins, minerals, Fatty acids, amino acids, and the like), laxatives, analgesics, antacids, H2 receptor antagonists, antidiarrheals, decongestants, antitussives, antiemetics, antimicrobials, antimicotics, antivirals, expectorants, anti-inflammatory agents, antipyretics, their pharmaceutically acceptable salts and mixtures thereof. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases including but not limited to: organic bases and inorganic bases. Salts derived from inorganic ises include sodium, potassium, lithium, ammonia, calcium, magnesium, ferrous, zinc, manganese, aluminum, ferric, manganic salts and the like. Salts derived from pharmaceutically acceptable non-toxic organic bases include salts of primary, secondary, tertiary and quaternary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange reams, such as triethylamine, tripropylamine, 2- di-ethylaminoethanol, 2-d? et? lam? noethanol, lysine, arginine, histidine, caffeine, proca, N-ethylpipepdma, hydramoam, choline, betaine, ethylenediamine, glucose ina, methyl glycol, theobromine, purines, piperaz, piperidine, polyarmne resins and the like. Examples of decongestants useful in the compositions of the present invention include pseudoephedrine, phenylpropanelapuna, phenyleptophan and ephedrine, their pharmaceutically acceptable salts and mixtures thereof. Examples of antitussives useful in the compositions of the present invention include dextromethorphan, clopedianol, carbetapentane, caramiphen, noscapma, diphenhydram, codema, hydrocodone, hydro orphan, their pharmaceutically acceptable salts and mixtures thereof. Examples of expectorants (also known as rnucolytic agents) useful in the present invention include: guaifemsma, terpine hydrate, ammonium chloride, N-acetylcieteine, and ambroxol, their pharmaceutically acceptable salts and mixtures thereof. Examples of analgesics useful in the present invention include: morphine, codeine, eperidine, pentazocine, propoxyphene, acetaminophen, allopurinol, acetylsalicylic acid, choline ealicylate, ketoprofen, magnesium silicate, fenoprofen, ibuprofen, indomethacin, naproxen, and many others and their pharmaceutically acceptable eleates and mix thereof. Example of antihistarnínicoe útilee in the present invention include: bro ofenirairamine, chlorpheniramine, clernastine, dexchlorphenirane, diphenhydramine, doxylamine, prornetacin, terfenadine, tripolidine and rn? Chae others and their pharmaceutically acceptable salts and mixtures of the same. Analgesics, deecongeetionantes, antihistarninicos, expectorantee and antitueivoe, as well as their acceptable dosage scales are described in the Patent -North American No. 4,783,465 for S? Nshine and other, issued on November 8, 1988, and US Patent No. 4,619,934 for Sunehine and another issued October 28, 1986, all of which are incorporated herein by reference. Examples of gastrointestinal agents suitable for use in the present invention include anticholinergics, which include atropine, clidinium and dicyclomin; antacids including aluminum hydroxide, bismuth subsalicylate, calcium carbonate and rnagaldrate; antagonietae of the H2 receptors that include: cimetidine, famotidine, nizatidine ranitidine; laxatives that include: phenolphthalein and caeantrol; and antidiarrheal agents that include: diphenoxylate and loperamide. Additional examples of analgesics, decongestants, antitussives, expectorants and antihistamines suitable as bronchodilators, anorectics, laxatives, anti-ethical, antimicrobial, antibacterial, anti-icotic, anti-inflammatory, antiviral, antipyretic, nutritional supplements, anticholinergic, antacids, H2 receptor antagonists , antidiarrheals, and other gaetrointeceptive compounds and their acceptable dosage scales are described in "Remington's Pharmaceutical Sciences," pp. 734-789, 791-799, 861-868, 907-945, 875-888, 1002-134, 1098-1121, 1124-1131, 1173-1224, 1232-1241, (Alfonso R. Gennaro, editor) (lBth ed. 1990), incorporated in the preamble as a reference.

NON-ESSENTIAL COMPONENTS Lae pereonae skilled in the art will quickly realize that many other ingredients may be suitable for inclusion in the present invention. Non-essential components include, but are not limited to: colorant agent; flavoring agents, which include: vanilla, cherry, grape, orange, peppermint, peppermint, anise, blueberry, raspberry, banana, chocolate, caramel, freea, lemon, urn, menthol and ProeweetTM MM50 (a combination of natural and artificial flavors) and propylene glycol, available from Virginia Daré Extract Co., Inc., Brooklyn, NY); sweeteners, which include saccharin, dextrose, levulose, sucrose, cyclamate, mannitol and aspartate together with many others; suspending agents including xanthine gum, acacia gum, carboxy etulcellulose, starch and methyl cellulose; conservatives; release agents, including polysorbate 80, sodium lauryl sulfate, vegetable oils and magnesium stearate; and water. Another preferred non-essential component of the present invention is a cooling agent or a combination of cooling agents. Suitable refreshing agents are those described in US Patent 4,136,163 of January 23, 1979, to Uatson et al., US Patent 4,230,688, October 28, 1980, to Rowsell et al. And US Patent 4,032,661 to Rowsell et al., Which are incorporated herein. herein as a reference, refreshing agents , particularly preferred include N-ethyl-p-rnentan-3-carboxamide (US-3 supplied by Sterling Organics), taught by the above incorporated patent, US Pat. No. 4,136,163, and N-2,3-trirnethyl-2- isopropylbutanamide, which is commercially available as or LJS-23 from Uilkinson Sword Limited and taught by the previously incorporated US Patent 4,230,688. Another particularly preferred cooling agent is 3,1-menthoxypropane-1,2-diol (TK-10, surinified by Takaeago Perfurnery Co., Ltd., Tokyo, Japan). This material is described in detail in US Pat. No. 4,459,425 of July 10, 1984 for Amano et al., And is incorporated herein by reference. The good-tasting pharmaceutical adsorbate compositions of the present invention are prepared using principles and methodologies recognized in the art of mixing the ingredients and choosing the type of mixing equipment to be used. When certain taste masking agents such as magnesium minosilicate are used, there is a potential for adverse interactions between the agent and different cationic multiple charge drugs (eg chlorpheniramine), which results in poor drug dissolution; It is critical that certain measures be followed to ensure the effective dissolution of the drug. Such a situation is described in McGinty, J.U. and Lach, J.L., "In vitro Adsorption of Various Pharmaceuticals to Montmorillonite", Jour. of Pharm. ,., ---? ci. , 65, 896-902 (1976), which is incorporated in the preamble as reference. The term "multi-charge cationic drugs" as used herein means compounds containing more than one positively charged substituent. Crucial steps include maintaining the pH on a scale equal to that of p > Ka of the multi-charge cationic drug or drugs and, additionally, reserve the addition of multiple charge cationic drugs until after addition of at least one other cationic compound. Good tasting pharmaceutical compositions that bind alternative taste masking agents are similarly prepared using principles and methodologies recognized in the art. A more detailed description of these preparation methods is described in the examples recorded below. After forming the matrix of the present invention, it is incorporated into an orally acceptable pharmaceutical carrier that rapidly disintegrates in aqueous solutions. Suitable vehicles can incorporate effervescent or water-dispersible substances which are dried in dosage forms which disintegrate rapidly upon contact with an aqueous liquid. The appropriate effervescent technology is described in Chapter 6 of "Pharmaceutical Dosage Forms; Tablets" Vol.

I 2nd ed., A Lieberman ed. , 1989, Marcel Dek er, Inc., incorporated herein by reference. The aforementioned compositions can be formed using any of ^ a multitude of techniques and equipment for solid dosing training. Formulation methods of solid dosages are well known in the art and may use any suitable method. Additional information regarding the formulation of solid dosages can be found in "Remington's Ph rmaceutical Sciences", pp 1633-1664, (Alfonso R. Gennaro, Editor) (18th ed 1990). Alternatively, the compositions of the present invention can be achieved by incorporation of the matrix in a freeze-dried form. Freeze drying or freeze drying facilitates the disintegration of the composition by forming the dry composition in an open matrix network. In most cases, this results in rapid penetration by the aqueous medium, promoting timely release of the active ingredients of the product. Suitable methods of freeze drying are well known in the art and commonly used. Any suitable conventional method of freeze drying can be used. A preferable method of freezing and drying is to rapidly freeze the composition and then dry the composition to a final moisture content of about 2 to 5%. Suitable production methods and freeze drying are taught in US Patent 4,642,903 of February 17, 1987 to Davies, US Pat. No. 4,946,684 of Aug. 7, 1990, to Blanck et al., US Patent 4,305,502 and 4,371,516 issued December 15, 1981 and February 1 ^, of 1983 respectively for Gregory and others, and Patent North American, 5,188,825 of February 23, 1993, for lies and others; all of which are incorporated herein by reference. Similarly, the compositions of the present invention can be vacuum dried. Vacuum drying includes at least partial drying of the co-locations at temperatures above the decomposition temperature. On the other hand, freeze drying includes the drying of compositions at temperatures below the setting temperature of the composition. Any suitable method of vacuum drying can be used. Vacuum drying processes are described in US Pat. No. 5,298,261 to Pebley et al., Issued March 29, 1994, incorporated herein by reference. Another form of rapid solution technology that may be applicable to the present invention is a liquid / liquid extract developed by Janssen Pharmaceutica Inc. and is identified by the Quicksolv ™ brand. This technology is fully described in U.S. Patent 5,215,756, incorporated herein by reference.

EXAMPLES The following examples will further describe and demonstrate the modalities within the scope of this , - • - invention. The examples are given solely for the purpose of illustration and are not designed as or limitations of the present invention, since many variations are possible without departing from the spirit and scope of the invention. r EXAMPLE I Ingredient% p / p Magnesium stearate 0.50000 Sorbitol compressible 44.17000 Silicon dioxide1 0.10000 Anhydrous citric acid 6.25000 Pretreated sodium bicarbonate2 18.75000 Chlorpheniramine maleate 0.80000 HCl-Phenylpropanolamine 5.00000 Xanthine rubber 24.00000 Orange flavor 0.40000 0.30000 cream flavor i Available as Cab-o-sil from Cabot Corporation, Tuscola, - > = - Illinois 2 Pretreatment is developed by heating overnight in a forced air oven (Despatch, rnodel • LDB_l-23) at 66 ° C.

In a container of adequate size, with mixer LigthinTM 8 (model No. TS2010 (or a high cut hogenizer set at 30 to 50 RPM)), mixing at approximately 250 to 1000 RPM, add the following agents allowing each to be dissolved before adding the following: water (add one) - enough water to uniformly wet chlorpheraine maleate and xanthine gum to mix, water will be removed by drying), chlorpheniramine maleate, xanthine gum. Shake vigorously (250 to 1000 RPM) for 45 minutes. Dry the mixture in an oven at 45 ° C for 12 hours or until the mixture dries and the water has been removed. Grind the dry mix to a particle size suitable for compression. In a separate suitable size container, after the same procedure, combine the phenylpropanolamine hydrochloride with xanthine gum. Then, dry mix through conventional mixing methods (eg mixer V) the above precomplexes of xanthine gum with magnesium stearate, compressible sorbitol, and silicon oxide, citric acid anhydrous, pretreated sodium bicarbonate and taste ^ .Orange and cream. Using a conventional tableting machine in a controlled humidity room (<25% RH), compress tablets to a weight of 500 mg tablets. Protect the tablets from moisture by sealing in glass jars or in cavities or foil blisters. Administration of 2 tablets is the usual and customary dosage.

EXAMPLE II Ingredient% p / p Magnesium Stearate 0.50000 Sorbitol Compressible 56.76000 Silicon Dioxide * 0.10000 Anhydrous Citric Acid 6.25000 Pretreated Eodium Bicarbonate2 18.75000 HBr-Dextro Etorphane 4.00000 Methylmethacrylic Copolymer3 13.34000 Lime / Lemon flavor 0.30000 1 Available as Cab-O-Silber from Cabot Corporation, Tuscola, Illinois . 2 The pretreatment is carried out by heating overnight in a forced air oven (Deepatch, Model LDB-1-23) at 66 ° C. / --_ 3 Available as Eudragit * L30D from Rohm and Haas.

In a properly sized container, with Lightnin ™ mixer (model No. TS2010 (or a high cut homogenizer set at 30 to 50 RPM)) mix at approximately 250 - 1000 RPM, add the following agents allowing to dissolve each one before adding the following: water (add a sufficient amount of water to uniformly wet the HBr-dextornethorphan and methyl ethacrylate copolymer to mix, the water will be removed by drying), HBr-dextromethorphan, methylmethylpolymer. Mix vigorously (250 to 1000) RPM) for 45 minutes. Dry the mixture in an oven at 45 ° C for 12 hours or until the mixture dries and the water is removed. Grind the dry mix to a particle size suitable for compression. Mix dry with conventional mixing methods (eg mixer V) dextromerfano bromihydrate and the pre-complex of methylmethacrylic polymer with gaseous stearate, compressible eorbitol, eilicon oxide, citric acid anhydrous, pretreated eodium bicarbonate, and lirna / lirnón flavor . Using a tablet press in a controlled humidity room (<25% RH), compress the tablets to 500 mg tablet weight. Protect the moisture tablets by sealing them in glass jars or in cavities or folio blisters. The administration of two tablets is the normal and adequate dosage.

EXAMPLE III Ingredient% p / p Citric acid, anhydrous, fine 6.25000 Pretreated eodium bicarbonate 1. 18.75000 Magnesium aluminoeilicate2 42.00000 HCl- Pseudoephedrine 6.00000 Chlorpheniramine maleate 0.40000 Methyl salicylate 0.20000 Magnesium stearate 0.50000 Mentol 0.50000 N-ethyl-p-menthane-3-carboxamide3 0.80000 Monoammonium glycyrrhizate * 0.06000 Sodium saccharine 0.05000 Silicon dioxide 0.50000 Vanilla cream 0.03000 Mammole 23.18000 The pre-treatment is carried out by heating overnight in a forced air oven (Despatch, Model LDB-1-23) at 66 ° C. 2 Available as Veegu HS from R.T. Vanderbit, Norwalk, CT: 3 Available as US-3, its introduced by Sterling Organics. 4 Available as Magnasweet 185 supplied by McAndrews 8 Forbes, Camden, NJ.

In a container of adequate size, with mixer LightnintM (model No. TS2010 (or a high-cut homogenizer -this is 30 to 50 RPM)) mix at approximately 250 to 1000 RPM, heat 800 rnl of purified water at 54 ° C. Add 43.75 gr of VeegumRhs while Continue mixing and heating the solution to 71 ° C, reduce the heat to approximately 38 ° C and mix for 2 hours Add pseudofedrine hydrochloride slowly and heat to 66 ° C and add additional water if necessary Mix for 2 hours Add the mixture to a Teflon or stainless steel tray and dry for 12 hours at 45 ° C or until the mixture dries, grind the dry mix to a suitable particle size for compression, dry dry by conventional mixing methods. (eg V-blender), the precoated Veegum® HS / pseudoephedrine hydrochloride, with chlorpheniramine maleate, citric acid (anhydrous), pretreated sodium bicarbonate, aspartame, methyl salicylate, nagnesium stearate, mannitol, glyceride Rnonoammonium izate, sodium saccharin, silicon dioxide, N-ethyl-p-menthane-3-carboxamide, menthol and savor vanilla cream. Using a normal tableting machine using a controlled humidity room (<25% RH), compress the tablets to a 500 g tablet weight. Protect the tablets from moisture by sealing them in glass jars or in cavities or folio blisters. Administration of two tablets is the usual and customary dosage.

EXAMPLE IV Ingredient% p / p Magnesium aluminosilicate 8.48900 Lopera, 2.44000 Polisorbate 80 0.04000 Sodium saccharine 0.05200 Aspartarne 0.05200 Sucrose 14.00000 Mannitol 12.25500 Novagel RCN-15 1.60000 Lemon flavor 0.47200 Vanilla cream 0.15000 Citric acid 0.45000 Purified water c.s.p. 100 EXAMPLE V Ingredient% p / p Magnesium Alminosilicate 4.00000 Bismuth subsalicylate 21.69930 Polysorbate 80 0.03500 Sodium saccharine 0.04550 Aspart me 1.00000 Sucrose 2.00000 Manitol 4.15000 Novagel RCN-15 1.40000 Strawberry flavor 0.54600 Vanilla cream 0.54990 Citric acid 0.06690 Klucel EF NF2 0.25200 Antifoamer AF3 0.21000 Purified water c.s.p. 100 EXAMPLE VI Ingredient% £ / £ Magnesium aluminosilicate 4.00000 Si ethicone 3.50000 Polysorbate 80 0.03500 Sodium saccharine 0.04550 Aspartame 0.04550 Sorbitol 0.70000 Sucrose 8.25000 Mannitol 16.29800 Novagel RCN-15 1.40000 Cherry flavor 0.19460 Vanilla cream 0.24780 Citric acid 0.28320 Antifoam AF3 0.21000 • Purified water Csp100 Supplied by FMC Corporation, Philadelphia, Pa. 2 Supplied by AQUALON, Hopewell, Va.-3 supplied by Dow Corning, Midland, Mich. Examples IV-VI are additional examples of combinations used in the treatment of gastrointestinal disease symptoms in humans and are manufactured substantially similar to Example III. The administration of two tablets is the usual and customary dosage.

Claims (17)

NOVELTY OF THE INVENTION CLAIMS

1. - An oral pharmaceutical composition comprising, (a) an unbreakable drug matrix comprising, i) a taste masking agent; and ii) a safe and effective amount of a pharmaceutically active ingredient; and (b) an orally acceptable pharmaceutical carrier wherein said pharmaceutically acceptable carrier rapidly disintegrates in aqueous solution without the need for mastication and wherein said composition provides for an immediate release of a pharmaceutically active ingredient.

2. A pharmaceutical composition according to claim 1, further characterized in that said vehicle is a freeze-dried matrix, an effervescent system, to a liquid / liquid extract system.

3. A pharmaceutical composition according to claim 2, further characterized in that the composition additionally contains one or more sabotage agents.

4. A pharmaceutical composition according to claim 3, further characterized in that the composition additionally contains one or more sweetening agents.

5. A pharmaceutical composition according to claim 4, further characterized in that the composition contains additional one or more release agents.

6. - A pharmaceutical composition according to claim 5, further characterized in that the composition additionally contains one or more cooling agents.

7. A pharmaceutical composition according to claim 6, further characterized in that the agent sabopzante is selected from the group consisting of menthol, entapiperita, yervabuena, raspberry, cherry, orange, vanilla, anise, bilberry, banana, chocolate, caramel, strawberry, lemon, lime, grape and mixtures thereof.

8. A pharmaceutical composition according to claim 7, further characterized in that the sweetening agent is selected from the group consisting of sodium saccharin, aspartame, onoammonium glycyrrhizate, sucrose, mannitol and mixture of the rnismoe.

9. A pharmaceutical composition according to claim 8, further characterized in that the release agent is selected from the group consisting of polysorbate 80, eodium lauryl sulfate, magnesium stearate and mixtures of the rnismoe.

10. - A pharmaceutical composition according to claim 9, further characterized in that the cooling agent is selected from the group consisting of: 3, 1-methoxyphen-1, 2-d-ol, N-eti lp- methan-3-carboxamide, N-2, 3-tprnet? l-2-ieopro? butanarnide and mixtures thereof.

11. - A pharmaceutical composition according to claim 10, further characterized in that the pharmaceutical active ingredients are selected from the group of active pharmaceutical ingredients consisting of acetaminophen, ibuprofen, dextro etorphane bromihydrate, doxyl ina succinate, pseudoepheryl hydrochloride , phenylpropanolamine hydrochloride, chlorpheniramine maleate, guaifenisin, tpprolidine hydrochloride, diphenhydramine hydrochloride, and mixtures thereof.

12. A pharmaceutical composition according to claim 11, further characterized in that the pharmaceutically active ingredients are pseudoephedrine hydrochloride and chlorphenira maleate ina.

13. A pharmaceutical composition according to claim 1, further characterized in that the pharmaceutically active ingredient is a gastrointestinal agent.

14. A method of treating the symptoms of a respiratory disease by administering a safe and effective amount of a pharmaceutical composition according to claim 1.

15. A method of treating the symptoms of a gastrointestinal tract by administering a A safe and effective amount of a composition according to claim 13.

16. A method of treating allergy-like allergy or smtornae by administering a safe and effective amount of a composition according to claim 11.

17. - A method of treating allergy or eintomae like allergy by administering a safe and effective amount of a composition according to claim 12.