WO1994020074A1 - Adsorbate compositions - Google Patents
Adsorbate compositions Download PDFInfo
- Publication number
- WO1994020074A1 WO1994020074A1 PCT/US1994/001916 US9401916W WO9420074A1 WO 1994020074 A1 WO1994020074 A1 WO 1994020074A1 US 9401916 W US9401916 W US 9401916W WO 9420074 A1 WO9420074 A1 WO 9420074A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- composition according
- mixtures
- group
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
Definitions
- the present invention relates to good-tasting, adsorbate composi ⁇ tions containing a single or a combination of active ingredients.
- the present invention relates to pharmaceutical adsorbate compositions having improved taste containing one or more of active ingredients comprising: a) a clay component comprising:
- magnesium trisilicate and 2) magnesium aluminum silicate in a ratio of from about 1 to 100 to about 100 to 1; and b) a safe and effective amount of one or more pharmaceutically acceptable compounds.
- the present invention also relates to a method of treating respiratory disorders, cough, cold, cold-like and/or flu symptoms associated with the common cold, gastrointestinal disorders and allergies; comprising the administration of a safe and effective amount of the compositions of the present invention.
- safety and effective amount is an amount that is effective to mitigate and/or treat the symptoms for which the active ingredient is indicated in a human without undue adverse side effects commensurate with a reasonable risk/benefit ratio.
- compositions of the present invention contain essential components as well as various nonessential components as indicated below.
- the first essential component of the present invention is a safe and effective amount of magnesium aluminum silicate (or aluminum magnesium silicate) of the formula Al 2 Mg0 8 Si 2 .
- magnesium aluminum silicate occurs naturally in such smectite minerals as colerainite, saponite, sapphirine, sheridanite and zebedassite.
- Refined magnesium aluminum silicates, such as Veegum ® N, magnesium aluminum silicate, is available from and manufactured by R.T. Vanderbilt Company, Inc., Norwalk, CT.
- a typical chemical analysis of Veegum ® N is as follows:
- Silicon dioxide 63.0 Magnesium oxide 10.5 Aluminum oxide 10.5 Ferric oxide 0.9 Calcium oxide 2.3
- compositions of this invention typically comprise from about 0.01% to about 50%, preferably from about 0.1% to about 25%, more preferably from about 1.0% to about 10% and most preferably from about 1.0% to about 5%, by weight of a magnesium aluminum silicate.
- magnesium aluminum silicate adds additional taste masking ability by adsorbing any active compounds that leach from the magnesium trisili ⁇ cate.
- magnesium aluminum silicate retards the dissolution of the invention's active compounds. It has also been theorized that varying the amount of magnesium aluminum silicate changes the final composition's dissolu ⁇ tion rate. Dissolution and magnesium aluminum silicate seem to be directly related.
- a second essential component of the present invention is a safe and effective amount of magnesium trisilicate of the formula Mg 2 0 8 Si 3 .
- Magnesium trisilicate occurs naturally in such materials as meer- schau , parasepiolite and sepiolite.
- Magnesium trisilicate can also be prepared by precipitating sodium silicate with magnesium sulfate, as disclosed in U.S. Patent 3,272,594, September 13, 1966, herein incorporated by reference.
- compositions of this invention typically comprise from about 0.01% to about 90%, preferably from about 0.1% to about 50% and most preferably from about 1.0% to about 10%, by weight of magnesium trisilicate.
- a form of magnesium trisilicate suitable for use in the present invention is dextromethorphan hydrobromide adsorbate available from Roche Pharmaceuticals, Nutley New Jersey, further defined by U.S. Patent 3.085.942. April 16, 1963, to Clifton et al . and herein incorporated by reference.
- U.S. Patent 4.581.232. April 8, 1986, to Peters et al . discloses magnesium trisilicate as a medicament adsor ⁇ bate and is herein incorporated by reference.
- Pharmaceutically acceptable actives useful in the present invention include any chemical material or compound suitable for oral administration and having a pharmacological action.
- the pharmaceuti ⁇ cally acceptable active materials or compounds useful in the present invention should be compatible with the other essential ingredients and compatible in combination with other included active materials or compounds.
- These pharmaceutically acceptable active materials or compounds are present at a level from about 0.01% to about 75%, preferably from about 0.1% to about 50%, more preferably from about 1.0% to about 25% and most preferably from about 1.0% to about 10%.
- Pharmaceutically acceptable active materials or compounds include, but are not limited to: bronchodilators, anorexiants, antihistamines, nutritional supplements (such as vitamins, minerals, fatty acids, a ino acids, and the like), laxatives, analgesics, antacids, H 2 - receptor antagonists, antidiarrheals, decongestants, antitussives, antinauseants, antimicrobials, antifungals, antivirals, expectorants, anti-inflammatory agents, antipyretics and pharmaceutically acceptable salts and mixtures thereof.
- salts refers to salts prepared from pharmaceutically acceptable non-toxic bases including inorganic bases and organic bases. Salts derived from nonorganic bases include sodium, potassium, lithium, ammonia, calcium, magnesium, ferrous, zinc, manganous, aluminum, ferric, manganic salts and the like.
- Salts derived from pharmaceutically acceptable organic non- toxic bases include salts of primary, secondary, tertiary and quar- ternary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as triethylamine, tripropylamine, 2-dimethylaminoethanol , 2-diethyl- aminoethanol , lysine, arginine, histidine, caffeine, procaine, N-ethylpiperidine, hydrabamine, choline, betaine, ethylenediamine, glucosa ine, methylglycamine, theobromine, purines, piperazine, piperidine, polyamine resins and the like.
- basic ion exchange resins such as triethylamine, tripropylamine, 2-dimethylaminoethanol , 2-diethyl- aminoethanol , lysine, arginine, histidine, caffeine, procaine, N
- decongestants useful in the compositions of the present invention include pseudoephedrine, phenylpropanolamine, phenylephrine and ephedrine, their pharmaceutically acceptable salts, and mixtures thereof.
- expectorants also known as mucolytic agents
- examples of expectorants include glyceryl guaiacolate, terpin hydrate, ammonium chloride, N-acetylcysteine, and ambroxol , their pharmaceuti- cally acceptable salts, and mixtures thereof.
- analgesics useful in the present invention include: morphine, codeine, meperidine, pentazocine, propoxyphene, acetamino ⁇ phen, allopurinol, acetylsalicylic acid, choline salicylate, ketopro- fen, magnesium silicate, salsalate, fenoprofen, ibuprofen, indometha- zin, naproxen, and many others and their pharmaceutically acceptable salts and mixtures thereof.
- Analgesics, decongestants, expectorants and antitussives, as well as their acceptable dosage ranges are described in U.S. Patent 4,783,465 to Sunshine et al . , issued November 8, 1988, and U.S. Patent 4,619,934 to Sunshine et al . , issued October 28, 1986, which are incorporated by reference herein.
- antihistamines useful in the present invention include: brompheniramine, chlorpheniramine, clemastine, dexchlor- pheniramine, diphenhydramine, doxylamine, promethazine, terfenadine, tripoliaine and many others and their pharmaceutically acceptable salts and mixtures thereof.
- gastrointestinal agents suitable for use in the present invention include: antichol inergics, including atropine, clidinium and dicyclomine; antiacids, including aluminum hydroxide, bismuth subsalicylate, calcium carbonate and magaldrate; H 2 -receptor antagonists including: cimetidine, famotidine, nizatidine and ranitidine; laxatives, including: phenolphthalein and casanthrol ; and antidiarrheals including: diphenoxylate and loperamide.
- antichol inergics including atropine, clidinium and dicyclomine
- antiacids including aluminum hydroxide, bismuth subsalicylate, calcium carbonate and magaldrate
- H 2 -receptor antagonists including: cimetidine, famotidine, nizatidine and ranitidine
- laxatives including: phenolphthalein and casanthrol
- antidiarrheals including: diphenoxylate and loperamide
- analgesics decongestants, anti ⁇ tussives, expectorants and antihistamines as well as bronchodilators, anorexiants, laxatives, antiemetics, antimicrobials, antibacterials, antifungals, anti-inflammatory agents, antivirals, antipyretics, nutritional supplements, antichol inergics, antacids, H 2 -receptors antagonists, antidiarrheals and other miscellaneous gastrointestinal compounds and their acceptable dosages ranges are described in Remington's Pharmaceutical Sciences, pp.
- Nonessential components include, but are not limited to: coloring agents; flavoring agents, including: vanilla, cherry, grape, orange, peppermint, spearmint, anise, blueberry, raspberry, banana, chocolate, carmel, strawberry, lemon, menthol and ProsweetTM M 50 (a combination of natural and artificial flavors and propylene glycol, available from Virginia Dare Extract Co., Inc., Brooklyn, NY); sweeteners, including saccharin, dextrose, levulose, sucrose, cyclamate, mannitol and aspartate, along with many others; suspending agents, including xanthum gum, acacia gum, carboxymethylcellulose, starch and methyl- cellulose; preservatives; releasing agents, including polysorbate 80, sodium lauryl sulfate, vegetable oils and magnesium stearate; and water.
- coloring agents including: vanilla, cherry, grape, orange, peppermint, spearmint, anise, blueberry, raspberry, banana, chocolate, carmel, strawberry, lemon, menthol and Pro
- Another preferred nonessential component of the present invention is a cooling agent or a combination of cooling agents.
- Suitable cooling agents are those described in U.S. Patent 4,136,163, January 23, 1979, to Watson et al . , U.S. Patent 4,230,668, October 28, 1980, to Rowsell et al . and U.S. Patent 4.032.661. to Rowsell et al . all herein incorporated by reference.
- a particularly preferred cooling agent is N-ethyl-p-menthane-3-carboxamide (WS-3 supplied by Sterling Organics), taught by the above incorporated U.S. Patent 4,136,163.
- Another particularly preferred cooling agent is 3-1-menthoxypropane
- nonessential components aid in maintaining the stability and aesthetic characteristics of the invention.
- METHOD OF MANUFACTURE Good tasting pharmaceutical adsorbate compositions of the present invention are prepared using art-recognized principles and methodo ⁇ logies in mixing the ingredients together and in choosing the type of mixing equipment to be used.
- the mixture must be dried and formulated into usable individual dosage forms. It is this process of water removal and formulation which determines the final products disintegration profile.
- a preferred method of water removal is freeze-drying.
- Freeze-drying or lyophilization facilitates disintegration of the composition upon introduction into the oral cavity. In most cases, this results in a rapid delivery of the product's active ingredients.
- Suitable methods of freeze-drying are well known in the art and commonly employed. Any suitable conventional method of freeze-drying or vacuum-drying may be utilized. A preferable method of freezing and drying is to fast freeze the composition and then dry the composition to a final moisture content of about 2% to about 5%. Suitable methods of freeze-drying and production are taught by U.S. Patent 4,642,903, February 17, 1987, to Davies, EP Patent Application 435,684, Al, published March 7, 1991, filed by R.P. Scherer Corporation, U.S. Patent 4.305.502. December 15, 1981 to Gregory et al . and U.S. Patent 4,642,903, February 17, 1987 to Davies et al . incorporated herein by reference.
- the composition could be dried by methods other than freeze-drying and formulated using any of a multitude of solid dosage forms using typical solid dosage forming equipment thereby producing a composition likely to have a different profile of disinte ⁇ gration.
- Methods of solid dosage formulation are well known in the art and any appropriate method may be utilized. Further information regarding solid dosage formulation can be found in Remington's Pharmaceutical Sciences, pp. 1633-1664, (Alfonso R. Gennaro, editor) (18th ed. 1990).
- ProsweetTM powder MM50 2 0.60000 sodium saccharin 0.15000 aspartame 0.30000 monoammonium glycyrrhizate 3 0.03000 sucrose 5.00000 mannitol 10.00000 3-1-menthoxypropane 1,2-diol 4 0.07000 N-ethyl-p-menthane-3-carboxamide 5 0.02000 dextromethorphan adsorbate 6 6.67000 menthol 0.28600 peppermint 0.18000 purified water q.s. to 100 available as Veegum ® N from R.T. Vanderbilt, Norwalk, CT. available from Virginia Dare Extract Co., Inc., Brooklyn, NY. available as Magnasweet 185 supplied by McAndrews & Forbes, Camden, NJ Available as TK-10 supplied by Takasago Perfumery Co.
- N-ethyl-p-methane-3-carboxamide 0.0100 mannitol 10.0000 sucrose 5.0000 xanthum gum 0.2000 chlorpheniramine maleate 0.1000 purified water q. ⁇ ;. to 100
- N-ethyl-p-methane-3-carboxamide 0.0100 mannitol 10.0000 sucrose 5.0000 xanthum gum 0.2000 purified water 2.0000 chlorpheniramine maleate 0.1000 purified water q.s. to 100
- Examples II-VI are further examples of combinations used in treating the symptoms of a respiratory illness or allergy in a human and are manufactured in a manner substantially similar to Example I. Administration of two tablets is the normal and customary dosage.
- Veegum® N 1.0000 magnesium trisilicate 6.7500 granulated calcium carbonate 1 42.8700
- Polysorbate 80 0.1000 citric acid 0.5500 sucrose 12.0000 mannitol 10.0000
- Granulated calcium carbonate containing 93.3% calcium carbonate, 6.3% glucose and 0.4% gelatin supplied by Whittaker, Clark & Daniels, Philadelphia, PA.
- Examples VII-X are combinations used for treating a gastrointestinal disorder in humans and are manufactured in a manner substantially similar to Example I. Administration of two tablets is the normal and customary dosage.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
An adsorbate composition comprising magnesium aluminum silicate, magnesium trisilicate and one or more pharmaceutically acceptable active ingredients.
Description
ADSORBATE COMPOSITIONS
TECHNICAL FIELD The present invention relates to good-tasting, adsorbate composi¬ tions containing a single or a combination of active ingredients.
BACKGROUND OF THE INVENTION Adsorbates have been used for many years, masking the untoward taste of many compounds. Examples using magnesium trisilicate as an adsorbate can be seen in U.S. Patent 3,085,942 to Clifton et al., April 16, 1963; and U.S. Patents 4.581.232. April 8, 1966; 4.632.821. December 30, 1986; 4.632.822. December 30, 1986; 4.623.823. December 30, 1986; 4.462.231. February 10, 1987; 4,643,898, February 17, 1987; 4,643.892. February 17, 1987; 4.647.449. March 3, 1987; 4.647.450. March 3, 1987; 4.647.459. March 3, 1987; 4.649.041. March 10, 1987; 4.650.663. March 17, 1987 to Peters et al .
Examples using aluminum-magnesium silicate as an adsorbate can be seen in U.S. Patents 4.711.774. December 8, 1987; 4.716.033. December 29, 1987; 4.758.424. July 19, 1988; 4.758.425. July 19, 1988; 4.761.274. August 2, 1988 to Denick, Jr. et al . , U.S. Patent 4.753.800. June 28, 1988 to Mozda and U.S. Patent 3.140.978. July 14, 1964 to Zentner.
While the prior art discloses the various adsorbates useful in masking the taste of active compounds, there is still a need for additional formulations providing improved taste-masking performance incorporating a single or multiple active ingredients. The present inventors have discovered that by combining adsorbates, a good tasting composition can be produced. While the prior art discloses several adsorbate compositions which mask the untoward flavor of active compounds,, these disclosures are only effective for relatively small amounts of an active ingredient. The present inventors have disco¬ vered a composition which is able to taste-mask a larger amount of active ingredient, or is capable of taste-masking several active ingredients used in combination. It is therefore an object of the present invention to provide a good-tasting adsorbate composition that contains a single or a combination of active ingredients. It is a further object to provide a method of reducing or abating the symptoms
associated with the common cold, respiratory disorders, gastrointes¬ tinal disorders and allergies with a good-tasting medicament adsorbate containing one or more active ingredients. Still a further object of the present invention is to provide a method of making a good-tasting, quick-dissolving, freeze-dried medicament adsorbate containing one or more active ingredients.
These objectives and additional objectives will become readily apparent from the detailed description which follows.
SUMMARY OF THE INVENTION The present invention relates to pharmaceutical adsorbate compositions having improved taste containing one or more of active ingredients comprising: a) a clay component comprising:
1) magnesium trisilicate; and 2) magnesium aluminum silicate in a ratio of from about 1 to 100 to about 100 to 1; and b) a safe and effective amount of one or more pharmaceutically acceptable compounds.
The present invention also relates to a method of treating respiratory disorders, cough, cold, cold-like and/or flu symptoms associated with the common cold, gastrointestinal disorders and allergies; comprising the administration of a safe and effective amount of the compositions of the present invention.
All percentages and ratios herein are by weight unless otherwise specified. Additionally, all measurements are made at 25βC unless otherwise specified.
By "safe and effective amount," as used herein, is an amount that is effective to mitigate and/or treat the symptoms for which the active ingredient is indicated in a human without undue adverse side effects commensurate with a reasonable risk/benefit ratio.
DETAILED DESCRIPTION OF THE INVENTION The compositions of the present invention contain essential components as well as various nonessential components as indicated below.
ESSENTIAL COMPONENTS Magnesium Aluminum Silicate
The first essential component of the present invention is a safe and effective amount of magnesium aluminum silicate (or aluminum magnesium silicate) of the formula Al2Mg08Si2. Magnesium aluminum silicate occurs naturally in such smectite minerals as colerainite, saponite, sapphirine, sheridanite and zebedassite. Refined magnesium aluminum silicates, such as Veegum® N, magnesium aluminum silicate, is available from and manufactured by R.T. Vanderbilt Company, Inc., Norwalk, CT. A typical chemical analysis of Veegum® N, is as follows:
Silicon dioxide 63.0 Magnesium oxide 10.5 Aluminum oxide 10.5 Ferric oxide 0.9 Calcium oxide 2.3
Sodium oxide 2.4
Potassium oxide 1.2
Ignition loss 7.5 having a combined density of 2.6mg/m2. The compositions of this invention typically comprise from about 0.01% to about 50%, preferably from about 0.1% to about 25%, more preferably from about 1.0% to about 10% and most preferably from about 1.0% to about 5%, by weight of a magnesium aluminum silicate.
Without being limited by theory, it appears that the addition of magnesium aluminum silicate adds additional taste masking ability by adsorbing any active compounds that leach from the magnesium trisili¬ cate. However, it also appears that the addition of magnesium aluminum silicate retards the dissolution of the invention's active compounds. It has also been theorized that varying the amount of magnesium aluminum silicate changes the final composition's dissolu¬ tion rate. Dissolution and magnesium aluminum silicate seem to be directly related.
U.S. Patent 4.761.274. August 2, 1988, to Denick, Jr. et al ; U.S. Patent 4.753.800, June 28, 1988, to Mozda, and U.S. Patent 3,140.978. July 14, 1964 to Zenteur disclose magnesium aluminum silicate as a medicament adsorbate and are herein incorporated by reference.
Magnesium Trisilicate
A second essential component of the present invention is a safe and effective amount of magnesium trisilicate of the formula Mg208Si3. Magnesium trisilicate occurs naturally in such materials as meer- schau , parasepiolite and sepiolite. Magnesium trisilicate can also be prepared by precipitating sodium silicate with magnesium sulfate, as disclosed in U.S. Patent 3,272,594, September 13, 1966, herein incorporated by reference.
The compositions of this invention typically comprise from about 0.01% to about 90%, preferably from about 0.1% to about 50% and most preferably from about 1.0% to about 10%, by weight of magnesium trisilicate. A form of magnesium trisilicate suitable for use in the present invention is dextromethorphan hydrobromide adsorbate available from Roche Pharmaceuticals, Nutley New Jersey, further defined by U.S. Patent 3.085.942. April 16, 1963, to Clifton et al . and herein incorporated by reference. U.S. Patent 4.581.232. April 8, 1986, to Peters et al . discloses magnesium trisilicate as a medicament adsor¬ bate and is herein incorporated by reference.
Without being limited by theory, it is believed that high levels of magnesium trisilicate impede subsequent disintegration and exhibit an disagreeable clay like taste. Pharmaceutically Acceptable Actives
Pharmaceutically acceptable actives useful in the present invention include any chemical material or compound suitable for oral administration and having a pharmacological action. The pharmaceuti¬ cally acceptable active materials or compounds useful in the present invention should be compatible with the other essential ingredients and compatible in combination with other included active materials or compounds. These pharmaceutically acceptable active materials or compounds are present at a level from about 0.01% to about 75%, preferably from about 0.1% to about 50%, more preferably from about 1.0% to about 25% and most preferably from about 1.0% to about 10%. Pharmaceutically acceptable active materials or compounds include, but are not limited to: bronchodilators, anorexiants, antihistamines, nutritional supplements (such as vitamins, minerals, fatty acids, a ino acids, and the like), laxatives, analgesics, antacids, H2- receptor antagonists, antidiarrheals, decongestants, antitussives,
antinauseants, antimicrobials, antifungals, antivirals, expectorants, anti-inflammatory agents, antipyretics and pharmaceutically acceptable salts and mixtures thereof.
The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases including inorganic bases and organic bases. Salts derived from nonorganic bases include sodium, potassium, lithium, ammonia, calcium, magnesium, ferrous, zinc, manganous, aluminum, ferric, manganic salts and the like. Salts derived from pharmaceutically acceptable organic non- toxic bases include salts of primary, secondary, tertiary and quar- ternary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as triethylamine, tripropylamine, 2-dimethylaminoethanol , 2-diethyl- aminoethanol , lysine, arginine, histidine, caffeine, procaine, N-ethylpiperidine, hydrabamine, choline, betaine, ethylenediamine, glucosa ine, methylglycamine, theobromine, purines, piperazine, piperidine, polyamine resins and the like.
Examples of decongestants useful in the compositions of the present invention include pseudoephedrine, phenylpropanolamine, phenylephrine and ephedrine, their pharmaceutically acceptable salts, and mixtures thereof.
Examples of antitussives useful in the compositions of the present invention include dextromethorphan, chlopedianol , carbeta- pentane, caramiphen, noscapine, diphenhydra ine, codeine, hydrocodone, hydromorphone, their pharmaceutically acceptable salts, and mixtures thereof.
Examples of expectorants (also known as mucolytic agents) useful in the present invention include glyceryl guaiacolate, terpin hydrate, ammonium chloride, N-acetylcysteine, and ambroxol , their pharmaceuti- cally acceptable salts, and mixtures thereof.
Examples of analgesics useful in the present invention include: morphine, codeine, meperidine, pentazocine, propoxyphene, acetamino¬ phen, allopurinol, acetylsalicylic acid, choline salicylate, ketopro- fen, magnesium silicate, salsalate, fenoprofen, ibuprofen, indometha- zin, naproxen, and many others and their pharmaceutically acceptable salts and mixtures thereof.
Analgesics, decongestants, expectorants and antitussives, as well as their acceptable dosage ranges are described in U.S. Patent 4,783,465 to Sunshine et al . , issued November 8, 1988, and U.S. Patent 4,619,934 to Sunshine et al . , issued October 28, 1986, which are incorporated by reference herein.
Examples of antihistamines useful in the present invention include: brompheniramine, chlorpheniramine, clemastine, dexchlor- pheniramine, diphenhydramine, doxylamine, promethazine, terfenadine, tripoliaine and many others and their pharmaceutically acceptable salts and mixtures thereof.
Examples of gastrointestinal agents suitable for use in the present invention include: antichol inergics, including atropine, clidinium and dicyclomine; antiacids, including aluminum hydroxide, bismuth subsalicylate, calcium carbonate and magaldrate; H2-receptor antagonists including: cimetidine, famotidine, nizatidine and ranitidine; laxatives, including: phenolphthalein and casanthrol ; and antidiarrheals including: diphenoxylate and loperamide.
Further examples of suitable analgesics, decongestants, anti¬ tussives, expectorants and antihistamines as well as bronchodilators, anorexiants, laxatives, antiemetics, antimicrobials, antibacterials, antifungals, anti-inflammatory agents, antivirals, antipyretics, nutritional supplements, antichol inergics, antacids, H2-receptors antagonists, antidiarrheals and other miscellaneous gastrointestinal compounds and their acceptable dosages ranges are described in Remington's Pharmaceutical Sciences, pp. 734-789, 791-799, 861-868, 907-945, 875-888, 1002-1034, 1098-1121, 1124-1131, 1173-1224, 1232- 1241, (Alfonso R. Gennaro, editor) (18th ed. 1990), herein incorpor¬ ated by reference.
NONESSENTIAL COMPONENTS Persons skilled in the art will quickly realized many other ingredients will be suitable for inclusion into the present invention. Nonessential components include, but are not limited to: coloring agents; flavoring agents, including: vanilla, cherry, grape, orange, peppermint, spearmint, anise, blueberry, raspberry, banana, chocolate, carmel, strawberry, lemon, menthol and ProsweetTM M 50 (a combination of natural and artificial flavors and propylene glycol, available from Virginia Dare Extract Co., Inc., Brooklyn, NY); sweeteners, including
saccharin, dextrose, levulose, sucrose, cyclamate, mannitol and aspartate, along with many others; suspending agents, including xanthum gum, acacia gum, carboxymethylcellulose, starch and methyl- cellulose; preservatives; releasing agents, including polysorbate 80, sodium lauryl sulfate, vegetable oils and magnesium stearate; and water.
Another preferred nonessential component of the present invention is a cooling agent or a combination of cooling agents. Suitable cooling agents are those described in U.S. Patent 4,136,163, January 23, 1979, to Watson et al . , U.S. Patent 4,230,668, October 28, 1980, to Rowsell et al . and U.S. Patent 4.032.661. to Rowsell et al . all herein incorporated by reference. A particularly preferred cooling agent is N-ethyl-p-menthane-3-carboxamide (WS-3 supplied by Sterling Organics), taught by the above incorporated U.S. Patent 4,136,163. Another particularly preferred cooling agent is 3-1-menthoxypropane
1,2-diol (TK-10 supplied by Takasago Perfumery Co., Ltd.), Tokyo,
Japan. This material is described in detail in U.S. Patent 4,459,425,
July 10, 1984 to Amano et al . and incorporated herein by reference.
These included nonessential components aid in maintaining the stability and aesthetic characteristics of the invention.
METHOD OF MANUFACTURE Good tasting pharmaceutical adsorbate compositions of the present invention are prepared using art-recognized principles and methodo¬ logies in mixing the ingredients together and in choosing the type of mixing equipment to be used.
After the ingredients of the present invention are combined, the mixture must be dried and formulated into usable individual dosage forms. It is this process of water removal and formulation which determines the final products disintegration profile. A preferred method of water removal is freeze-drying.
Freeze-drying or lyophilization facilitates disintegration of the composition upon introduction into the oral cavity. In most cases, this results in a rapid delivery of the product's active ingredients. Suitable methods of freeze-drying are well known in the art and commonly employed. Any suitable conventional method of freeze-drying or vacuum-drying may be utilized. A preferable method of freezing and drying is to fast freeze the composition and then dry the composition
to a final moisture content of about 2% to about 5%. Suitable methods of freeze-drying and production are taught by U.S. Patent 4,642,903, February 17, 1987, to Davies, EP Patent Application 435,684, Al, published March 7, 1991, filed by R.P. Scherer Corporation, U.S. Patent 4.305.502. December 15, 1981 to Gregory et al . and U.S. Patent 4,642,903, February 17, 1987 to Davies et al . incorporated herein by reference.
Alternatively, the composition could be dried by methods other than freeze-drying and formulated using any of a multitude of solid dosage forms using typical solid dosage forming equipment thereby producing a composition likely to have a different profile of disinte¬ gration. Methods of solid dosage formulation are well known in the art and any appropriate method may be utilized. Further information regarding solid dosage formulation can be found in Remington's Pharmaceutical Sciences, pp. 1633-1664, (Alfonso R. Gennaro, editor) (18th ed. 1990).
EXAMPLES The following examples further describe and demonstrate embodi¬ ments within the scope of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations are possible with departing from the spirit and scope of the inven¬ tion.
EXAMPLE I
Ingredients W/V% chlorphenirmaine maleate 0.13300 phenylpropanolamine HCL 0.83300 magnesium aluminum silicate1 2.00000 xanthum gum 0.20000 potassium sorbate 0.07500 polysorbate 80 0.10000
ProsweetTM powder MM502 0.60000 sodium saccharin 0.15000 aspartame 0.30000 monoammonium glycyrrhizate3 0.03000 sucrose 5.00000 mannitol 10.00000
3-1-menthoxypropane 1,2-diol4 0.07000 N-ethyl-p-menthane-3-carboxamide5 0.02000 dextromethorphan adsorbate6 6.67000 menthol 0.28600 peppermint 0.18000 purified water q.s. to 100 available as Veegum® N from R.T. Vanderbilt, Norwalk, CT. available from Virginia Dare Extract Co., Inc., Brooklyn, NY. available as Magnasweet 185 supplied by McAndrews & Forbes, Camden, NJ Available as TK-10 supplied by Takasago Perfumery Co.
5 Available as WS-3 supplied by Sterling Organics. available as 10% dextromethorphan hydrobromide adsorbate supplied by Roche Pharmaceuticals. In an appropriately sized container, with lightnin' mixer (model #TS2010 (or a high shear homogenizer set at 30 to 50 RPM)) mixing at approximately 250 to 1000 RPM, add the following agents allowing each to dissolve before adding the next: water, phenylpropanolamine HC1, dextromethorphan adsorbate, Veegum® N. Heat, using a hot plate, keeping solution at 77° C, and mix vigorously (250 to 1000 RPM) for 30 minutes. Turn heat off and allow mixture to cool to room temperature (25° C) while mixing for a minimum of an additional 15 minutes. Add monoammonium glycyrrhizate, ProsweetTM MM50, potassium sorbate, aspar- tame, sodium saccharin, WS-3 and peppermint. Separate from the above mixture, in an appropriate container, add polysorbate 80, TK-10, and menthol. Add this mixture to the original mixture.
Separately, dry blend mannitol, sucrose, and xanthum gum and add slowly to the original mixture. Separately dissolve chlorpheniramine maleate with a sufficient amount of water and add to the original mixture. Adjust the volume to 1.5000 liters and mix for 15 minutes. While the mixing continues place 1.5 ml of solution into molds and freeze-dry or vacuum-dry the composition. This process, in turn, provides a pharmaceutical adsorbate composition having improved taste. Administration of two tablets to an adult human is the normal and customary dosage for use in treating the symptoms of a respiratory illness or allergy.
EXAMPLE II
Inqredients W/V% phenylpropanolamine hydrochloride 0.6250 dextromethorphan adsorbate 5.0000
Veegum* N 2.0000 polysorbate 80 0.1000
ProsweetTM powder MM50 0.0600 aspartame 0.3000 sodium saccharin 0.0500 potassium sorbate 0.0750
3-1-methoxypropane 1,2-diol 0.0350
N-ethyl-p-methane-3-carboxamide 0.0100 mannitol 10.0000 sucrose 5.0000 xanthum gum 0.2000 chlorpheniramine maleate 0.1000 purified water q.< ;. to 100
EXAMPLE III
Inαredients W/YV phenylpropanolamine hydrochloride 0.6250 dextromethorphan adsorbate 5.0000
Veegum* N 1.0000 polysorbate 80 0.1000
ProsweetTM powder MM50 0.5000 onoammonium glycyrrhizate 0.0600 aspartame 0.3000 sodium saccharin 0.0500 potassium sorbate 0.0750
3-1-methoxypropane 1,2-diol 0.0350
N-ethyl-p-methane-3-carboxamide 0.0100 mannitol 10.0000 sucrose 5.0000 xanthum gum 0.2000 chlorpheniramine aleate 0.1000 purified water q.:s. to 100
EXAMPLE IV
Inoredients W/V% phenylpropanolamine hydrochloride 0.6250 dextromethorphan adsorbate 5.0000
Veegum* N 0.5000 polysorbate 80 0.1000
ProsweetTM powder MM50 0.5000 monoammonium glycyrrhizate 0.0600 aspartame 0.3000 sodium saccharin 0.0500 potassium sorbate 0.0750
3-1-methox propane 1,2-dlol 0.0350
N-ethyl-p-methane-3-carboxamide 0.0100 mannitol 10.0000 sucrose 5.0000 xanthum gum 0.2000 purified water 2.0000 chlorpheniramine maleate 0.1000 purified water q.s. to 100
EXAMPLE V
Inqredients W/V%
Veegum* N 2.0800 pheny propano amine hydrochloride 0.8330 dextromethorphan Adsorbate 6.6700 xanthum gum 0.2000 potassium sorbate 0.0750 polysorbate 80 0.1000
ProsweetTM 0.5000 sodium saccharin 0.0500 aspartame 0.3000 monoammonium glycyrrhizate 0.0300 sucrose 5.0000 mannitol 10.0000
Flavor 1.0500
3-1-methoxypropane 1,2-diol 0.0700
N-ethyl-p-menthane-3-carboxamide 0.0200 chlorpheniramine maleate 0.6670 purified water q.s. to 100
EXAMPLE VI
Ingredients W/V% chlorpheniramine maleate 0.1330 dextromethorphan adsorbate 6.6700 phenylpropanolamine hydrochloride 0.8330
Veegum® N 2.8980 xanthum gum 0.2000 potassium sorbate 0.7500 polysorbate 80 0.1000 Prosweet™ powder MM50 0.5000 sodium saccharin 0.1500 aspartame 0.3000 monoammonium glycyrrhizate 0.0300 sucrose 5.0000 mannitol 10.0000
3-1-methoxypropane 1,2-diol 0.0700
N-ethyl-p-methane-3-carboxamide 0.0200 flavor 0.3000 menthol 0.4000 color, FD&C Yellow #6 0.0024 color, FD&C Red #33 0.0033 purified water q.s. to 100 Examples II-VI are further examples of combinations used in treating the symptoms of a respiratory illness or allergy in a human and are manufactured in a manner substantially similar to Example I. Administration of two tablets is the normal and customary dosage.
EXAMPLE VII
Ingredients W/V% magnesium trisilicate 6.0000 Veegum® N 3.8640 loperamide 0.8000 xanthum gum 0.2000 potassium sorbate 0.7500 polysorbate 80 0.1000 ProsweetTM powder MM50 0.5000 sodium saccharin 0.1500 aspartame 0.3000
monoammonium glycyrrhizate 0.0300 sucrose 5.0000 mannitol 10.0000
3-1-methoxypropane 1,2-diol 0.0700
N-ethyl-p-methane-3-carboxamide 0.0200 flavor 0.3000 menthol 0.4000 color, FD&C Yellow #6 0.0024 color, FD&C Red #33 0.0033 purified water q.s. . to 100 EXWPLE VIII
Inαredients W/V magnesium trisilicate 6.0000
Veegum* N 4.8300 bismuth subsalicylate 1.7500 xanthum gum 0.2000 potassium sorbate 0.7500 polysorbate 80 0.1000
ProsweetTM powder MM50 0.5000 sodium saccharin 0.1500 aspartame ' 0.3000 monoammonium glycyrrhizate 0.0300 sucrose 5.0000 mannitol 10.0000
3-1-methoxypropane 1,2-diol 0.0700
N-ethyl-p-methane-3-carboxamide 0.0200 f1avor 0.3000 menthol 0.4000 color, FD&C Yel ow #6 0.0024 color, FD&C Red #33 0.0033 purified water q.s. . to 100 EXAMPLE IX
Inαredients W/V%
Veegum* N 4.1650 magnesium trisi icate 6.0000 cimetidine 1.0000
xanthum gum 0.2000 potassium sorbate 0.0750 polysorbate 80 0.1000
ProsweetTM powder MM50 0.5000 sodium saccharin 0.0500 aspartame 0.3000 monoammonium glycyrrhizate 0.0300 sucrose 5.0000 mannitol 10.0000 flavor 1.0500
3-1-methoxypropane 1,2-diol 0.0700
N-ethyl -p-methane-3-carboxamide 0.0200 purified water q.s. to 100
EXAMPLE X
Ingredients W/V%
Veegum® N 1.0000 magnesium trisilicate 6.7500 granulated calcium carbonate1 42.8700
Polysorbate 80 0.1000 citric acid 0.5500 sucrose 12.0000 mannitol 10.0000
Flavor 1.2500
FD&C Red #40 0.0050 purified water q.s. to 100
Granulated calcium carbonate containing 93.3% calcium carbonate, 6.3% glucose and 0.4% gelatin; supplied by Whittaker, Clark & Daniels, Philadelphia, PA.
Examples VII-X are combinations used for treating a gastrointestinal disorder in humans and are manufactured in a manner substantially similar to Example I. Administration of two tablets is the normal and customary dosage.
Claims
1. A composition comprising:
(a) a clay component comprising:
1) magnesium trisilicate; and
2) magnesium aluminum silicate in a ratio of from 1 to 100 to 100 to 1; and
(b) a safe and effective amount of one or more pharmaceutically acceptable compounds.
2. A composition according to Claim 1 wherein the clay component comprises from 1.0% to 99% of the total weight of the composition and wherein the clay component to active compounds is from 100 to 1 to 1 to 100.
3. A composition according to any of the preceding Claims wherein the clay component comprises from 0.01% to 90%, preferably from 1.0% to 10% by weight of magnesium trisilicate and from 0.01% to 50.0%, preferably from 1.0% to 5.0% by weight of magnesium aluminum silicate and wherein the pharmaceutically acceptable activ ) comprise from 0.01% to 85%, preferably from 1.0% to 10% of the total weight of the composition.
4. A composition according to any of the preceding Claims wherein the composition additionally contains one or more flavoring agents, preferably the flavoring agent is selected from the group consisting of menthol, peppermint, spearmint, raspberry, cherry, orange, vanilla, anise, blueberry, banana, chocolate, carmel, strawberry, lemon, grape and mixtures thereof.
5. A composition according to any of the preceding Claims wherein the composition additionally contains one or more sweetening agents, preferably the sweetening agent is selected from the group consisting of: sodium saccharin, aspartame, monoammonium glycyrrhizate, sucrose, mannitol and mixtures thereof.
6. A composition according to any of the preceding Claims wherein the composition additionally contains one or more releasing agents, preferably the releasing agent is selected from the group consisting of: polysorbate 80, sodium lauryl sulfate, magnesium stearate and mixtures thereof..
7. A composition according to any of the preceding Claims wherein the composition additionally contains one or more cooling agents, preferably the cooling agent is selected from the group consisting of: 3-1-methoxypropane 1,2-diol, N-ethyl-p-methane-3-carboxamide and mixtures thereof and wherein the pharmaceutically acceptable compound is selected from the group consisting of: an antitussive; an antinauseant; a nutritional supplement; a laxative; an appetite suppressant; an analgesic; an antiasthmatic; an antihistamine; a decongestant; an expectorant; an antacid; an antidiarrheal, a H2-Receptor antagonist and mixtures thereof.
8. A composition according to any of the preceding Claims wherein the pharmaceutically acceptable compounds is selected form the group consisting of loperamide, dextromethorphan, phenylpropanolamine and chlorpheniramine and mixtures thereof.
9. A composition according to any of the preceding Claims wherein the composition is freeze-dried.
10. A method of treating the symptoms of a respiratory illness by administering a safe and effective amount of a composition according to any of the preceding Claims.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3075493A | 1993-03-12 | 1993-03-12 | |
| US08/030,754 | 1993-03-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1994020074A1 true WO1994020074A1 (en) | 1994-09-15 |
Family
ID=21855850
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1994/001916 Ceased WO1994020074A1 (en) | 1993-03-12 | 1994-02-23 | Adsorbate compositions |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1994020074A1 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995011671A1 (en) * | 1993-10-28 | 1995-05-04 | The Procter & Gamble Company | Fast dissolving dosage forms containing magnesium aluminum silicate and multiple active ingredients |
| WO1996021431A1 (en) * | 1995-01-10 | 1996-07-18 | Warner-Lambert Company | Reduction of electrostatic forces between magnesium trisilicate adsorbates |
| US5811131A (en) * | 1997-02-19 | 1998-09-22 | Mackles; Leonard | Tasteless forms of basic drugs prepared by adsorption in situ |
| WO2000010527A1 (en) * | 1998-08-24 | 2000-03-02 | The Procter & Gamble Company | Oral mucoadhesive compositions containing gastrointestinal actives |
| EP1582221A1 (en) * | 2004-03-31 | 2005-10-05 | Chiesi S.A. | Pharmaceutical oral compositions with a taste masking effect |
| WO2007108010A3 (en) * | 2006-03-21 | 2008-05-22 | Jubilant Organosys Ltd | Taste masked pharmaceutical composition for oral solid dosage form and process for preparing the same using magnesium aluminium silicate |
| WO2014152481A1 (en) * | 2013-03-15 | 2014-09-25 | Materials Modification Inc. | Clay composites and their applications |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0526862A1 (en) * | 1991-08-06 | 1993-02-10 | VECTORPHARMA INTERNATIONAL S.p.A. | Solid pharmaceutical compositions for oral administration with prolonged gastric residence |
-
1994
- 1994-02-23 WO PCT/US1994/001916 patent/WO1994020074A1/en not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0526862A1 (en) * | 1991-08-06 | 1993-02-10 | VECTORPHARMA INTERNATIONAL S.p.A. | Solid pharmaceutical compositions for oral administration with prolonged gastric residence |
Non-Patent Citations (1)
| Title |
|---|
| REYNOLDS J.E.F.: "Martindale - The Extra Pharmacopoeia, 29th Edition", PHARMACEUTICAL PRESS, GB, LONDON,1989 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995011671A1 (en) * | 1993-10-28 | 1995-05-04 | The Procter & Gamble Company | Fast dissolving dosage forms containing magnesium aluminum silicate and multiple active ingredients |
| WO1996021431A1 (en) * | 1995-01-10 | 1996-07-18 | Warner-Lambert Company | Reduction of electrostatic forces between magnesium trisilicate adsorbates |
| US5626878A (en) * | 1995-01-10 | 1997-05-06 | Warner Lambert Company | Reduction of electrostatic forces between magnesium trisilicate adsorbates |
| US5811131A (en) * | 1997-02-19 | 1998-09-22 | Mackles; Leonard | Tasteless forms of basic drugs prepared by adsorption in situ |
| WO2000010527A1 (en) * | 1998-08-24 | 2000-03-02 | The Procter & Gamble Company | Oral mucoadhesive compositions containing gastrointestinal actives |
| EP1582221A1 (en) * | 2004-03-31 | 2005-10-05 | Chiesi S.A. | Pharmaceutical oral compositions with a taste masking effect |
| WO2007108010A3 (en) * | 2006-03-21 | 2008-05-22 | Jubilant Organosys Ltd | Taste masked pharmaceutical composition for oral solid dosage form and process for preparing the same using magnesium aluminium silicate |
| WO2014152481A1 (en) * | 2013-03-15 | 2014-09-25 | Materials Modification Inc. | Clay composites and their applications |
| US10046079B2 (en) | 2013-03-15 | 2018-08-14 | Materials Modification Inc. | Clay composites and their applications |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5560913A (en) | Pharmaceutical compositions | |
| US5196436A (en) | Dextromethorphan antitussive compositions | |
| US6027746A (en) | Chewable soft gelatin-encapsulated pharmaceutical adsorbates | |
| AU681672B2 (en) | Preparations containing silicon dioxide to improve the taste thereof | |
| US5780046A (en) | Oral formulations of S(+)-ibuprofen | |
| AU711853B2 (en) | Oral formulations of S(+)-etodolac | |
| PT1082106E (en) | Effervescent tablet for the sublingual, buccal and gingival administration of fentanyl | |
| JPH0818974B2 (en) | Medicinal adsorbate and its manufacturing method | |
| JPH10501235A (en) | Fast dissolving dosage form | |
| EP0725630A1 (en) | Fast dissolving dosage forms containing magnesium aluminum silicate and multiple active ingredients | |
| WO1994020074A1 (en) | Adsorbate compositions | |
| CA1333773C (en) | Antitussive liquid compositions containing phenol | |
| AU7525694A (en) | Hydrolyzed gelatin as a flavor enhancer in a chewable tablet | |
| US5888540A (en) | Pharmaceutical products | |
| CA2129676C (en) | Dextromethorphan antitussive compositions | |
| CA2175225C (en) | Gelatin capsule fill able to foam | |
| JPH0656677A (en) | Antacid composition | |
| WO1996029986A1 (en) | Antitussive microcapsules | |
| MXPA96006041A (en) | Dosage form of rapida disoluc | |
| HK1009940A (en) | Oral formulations of s(+)-etodolac | |
| HK1010096A (en) | Oral formulations of s( +) -ibuprofen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA FI JP NO |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase |
Ref country code: CA |