WO1994020074A1 - Compositions a base d'adsorbats - Google Patents

Compositions a base d'adsorbats Download PDF

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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
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WIPO (PCT)
Prior art keywords
composition
composition according
mixtures
group
pharmaceutically acceptable
Prior art date
Application number
PCT/US1994/001916
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English (en)
Inventor
Anne Marie Carella
Edward John Opiola
Original Assignee
The Procter & Gamble Company
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by The Procter & Gamble Company filed Critical The Procter & Gamble Company
Publication of WO1994020074A1 publication Critical patent/WO1994020074A1/fr

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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.

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Abstract

Composition à base d'adsorbats, comprenant du silicate d'aluminium-magnésium, du trisilicate de magnésium et un ou plusieurs ingrédients actifs acceptables pharmaceutiquement.
PCT/US1994/001916 1993-03-12 1994-02-23 Compositions a base d'adsorbats WO1994020074A1 (fr)

Applications Claiming Priority (2)

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US3075493A 1993-03-12 1993-03-12
US08/030,754 1993-03-12

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WO1994020074A1 true WO1994020074A1 (fr) 1994-09-15

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995011671A1 (fr) * 1993-10-28 1995-05-04 The Procter & Gamble Company Formes posologiques a dissolution rapide contenant du silicate de magnesium et d'aluminium et plusieurs ingredients actifs
WO1996021431A1 (fr) * 1995-01-10 1996-07-18 Warner-Lambert Company Reduction des forces electrostatiques entre adsorbats de trisilicate de magnesium
US5811131A (en) * 1997-02-19 1998-09-22 Mackles; Leonard Tasteless forms of basic drugs prepared by adsorption in situ
WO2000010527A1 (fr) * 1998-08-24 2000-03-02 The Procter & Gamble Company Compositions mucoadhesives renfermant des -ubstances actives au niveau gastro-intestinal
EP1582221A1 (fr) * 2004-03-31 2005-10-05 Chiesi S.A. Composition pharmaceutique pour masquer le gout de principes actifs
WO2007108010A2 (fr) * 2006-03-21 2007-09-27 Jubilant Organosys Limited Composition pharmaceutique à goût masque pour forme dosifiée orale solide et son procédé de préparation
WO2014152481A1 (fr) * 2013-03-15 2014-09-25 Materials Modification Inc. Composites d'argile et applications de ceux-ci

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0526862A1 (fr) * 1991-08-06 1993-02-10 VECTORPHARMA INTERNATIONAL S.p.A. Compositions pharmaceutiques solides pour l'administration orale à séjour gastrique prolongé

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0526862A1 (fr) * 1991-08-06 1993-02-10 VECTORPHARMA INTERNATIONAL S.p.A. Compositions pharmaceutiques solides pour l'administration orale à séjour gastrique prolongé

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
REYNOLDS J.E.F.: "Martindale - The Extra Pharmacopoeia, 29th Edition", PHARMACEUTICAL PRESS, GB, LONDON,1989 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995011671A1 (fr) * 1993-10-28 1995-05-04 The Procter & Gamble Company Formes posologiques a dissolution rapide contenant du silicate de magnesium et d'aluminium et plusieurs ingredients actifs
WO1996021431A1 (fr) * 1995-01-10 1996-07-18 Warner-Lambert Company Reduction des forces electrostatiques entre adsorbats de trisilicate de magnesium
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 (fr) * 1998-08-24 2000-03-02 The Procter & Gamble Company Compositions mucoadhesives renfermant des -ubstances actives au niveau gastro-intestinal
EP1582221A1 (fr) * 2004-03-31 2005-10-05 Chiesi S.A. Composition pharmaceutique pour masquer le gout de principes actifs
WO2007108010A2 (fr) * 2006-03-21 2007-09-27 Jubilant Organosys Limited Composition pharmaceutique à goût masque pour forme dosifiée orale solide et son procédé de préparation
WO2007108010A3 (fr) * 2006-03-21 2008-05-22 Jubilant Organosys Ltd Composition pharmaceutique à goût masque pour forme dosifiée orale solide et son procédé de préparation
WO2014152481A1 (fr) * 2013-03-15 2014-09-25 Materials Modification Inc. Composites d'argile et applications de ceux-ci
US10046079B2 (en) 2013-03-15 2018-08-14 Materials Modification Inc. Clay composites and their applications

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