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WO1999033445A1 - Composition de comprime - Google Patents

Composition de comprime Download PDF

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Publication number
WO1999033445A1
WO1999033445A1 PCT/US1997/024122 US9724122W WO9933445A1 WO 1999033445 A1 WO1999033445 A1 WO 1999033445A1 US 9724122 W US9724122 W US 9724122W WO 9933445 A1 WO9933445 A1 WO 9933445A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
agent
sugar
drug
tablet
Prior art date
Application number
PCT/US1997/024122
Other languages
English (en)
Inventor
Ashok Premchand Luhadiya
Stanislaus Valerain D'souza
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
Priority to EP97954647A priority Critical patent/EP1041965A1/fr
Priority to CA002317021A priority patent/CA2317021A1/fr
Priority to AU59046/98A priority patent/AU5904698A/en
Priority to PCT/US1997/024122 priority patent/WO1999033445A1/fr
Priority to JP11514272A priority patent/JP2000516263A/ja
Publication of WO1999033445A1 publication Critical patent/WO1999033445A1/fr

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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A61K47/585—Ion exchange resins, e.g. polystyrene sulfonic acid resin
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates

Definitions

  • the present invention relates to a tablet composition comprising a drug active.
  • compositions are given to the patient in many forms, such as liquid solutions including gels, emulsions, and suspensions; or in solid forms such as powders, granules, and tablets.
  • compositions administered in solid form, especially tablets, are usually intended to be swallowed whole or chewed.
  • a tablet e.g., the aged or children
  • tablets which can be readily ingested by chewing Such people desire tablets which dissolve immediately during chewing in the mouth.
  • Some of active ingredients which tend to exhibit the undesirable characteristic of bitter taste after oral administration by e.g., swallowing and/or chewing include e.g., acetaminophen, ampicillin, azithromycin, chlorpheniramine, cimetidine, dextromethorphan, diphenhydramine, erythromycin, ibuprofen, penicillin, phenylbutazone, psuedoephedrine, ranitidine, spironolactone, and theophylline for pharmaceutical compositions. See Keating U.S. Patent 2,990,332, Koff U.S. Patent 3,138,525, Raghunathan U.S. Patent 4,221 ,778, and Kelleher U.S. Patent 4,996,047.
  • the present invention is directed to a composition
  • a composition comprising a drug active; a thickening agent; and a sugar agent; wherein the composition is in solid form, and wherein the ratio of the thickening agent to the sugar agent causes the composition to become a paste when contacted with saliva.
  • solid tablet means a material which has a hard shape and is made by compressing granules pre-mixed into a predetermined shape or direct compression of ingredients contained, which includes, e.g., pills, lozenges, and troches.
  • paste means a material which is in smooth liquid form having higher or lower viscosity, e.g., gel form and cream form.
  • the present invention relates to a composition comprising a drug active; a thickening agent; and a sugar agent; wherein the composition is in solid form, and wherein the ratio of the thickening agent to the sugar agent causes the composition to become a paste when contacted with saliva. It is believed that tablets, when wetted with water, start penetration of water, swelling its structure, dissolving and destroying its shape, thereby the tablets change the structure into paste.
  • the tablet composition converts into a paste when contacted with saliva in the mouth.
  • a paste facilitates the user's swallowing the composition.
  • the paste provides an improved mouthfeel by, e.g., masking the bitter taste otherwise produced by the drug active and/or reducing any gritty sensation otherwise experienced by the user.
  • the ratio of the thickening agent to the sugar agent included in the composition is at least about 1 :7.
  • the paste of the composition prevents the user from experiencing the bitter taste of the drug active.
  • the combination of the thickening agent and sugar agent "suspends" the drug active in the paste form, such that the drug active does not fully contact the bitter sensing taste buds of the mouth.
  • conventional formulations have, in some cases, resorted to coating the drug active (e.g., drug resin complex) to prevent such a bitter taste sensation, such a formulation step is not necessary in the composition of the present invention.
  • an embodiment of the present invention comprising an uncoated drug resin complex would also result in little or no bitter taste sensation to user.
  • the composition can contain a higher concentration of drug actives in comparison with those included in the conventional tablets or lozenges.
  • the composition could contain from about 2 to about 6 times or more of an uncoated drug resin active, versus conventional compositions containing an uncoated resin composition.
  • the composition of the present invention includes a drug active.
  • drug active refers to an ingredient intended to be delivered (e.g., ingested by) the user for therapeutic treatment.
  • the drug active is a drug resin complex.
  • the drug resin complex contains an active ingredient which is conventionally used in pharmaceutical industries, in combination with an ionic exchange resin (e.g., cation), thereby delaying the release of the active ingredients during administration, for example, until the composition reaches the gastrointestinal tract.
  • Exemplary active ingredients which are suitable for the use in the drug resin complex may be acidic, basic or amphoteric.
  • acidic drugs useful herein include, but are not limited to, dehydrocholic acid, diflunisal, ethacrynic acid, fenoprofen, furosemide, gemfibrozil, ibuprofen, naproxen, phenytoin, probenecid, sulindac, theophylline, salicylic acid and acetylsalicylic acid.
  • Exemplary active ingredients which are basic include, but are not limited to, acetophenazine, amitriptyline, amphetamine, benztropine, biperiden, bromodiphenhydramine, brompheniramine. carbinoxamine, chlorcyclizine, chlorpheniramine, chlorphenoxamine, chlo ⁇ romazine, clemastine, clomiphene, clonidine, codeine, cyclizine, cyclobenzap ⁇ ne, cyproheptadine, desipramine, dexbrompheniramine, dexchlo ⁇ hemramine, dextroamphetamine, dextromethorphan, dicyclomine, diphemanil.
  • amphoteric drugs useful herein include, but are not limited to, aminocaproic acid, aminosalicylic acid, hydromorphone, isoxsuprine, levorphanol, melphalan, morphine, nalidixic acid, and paraaminosalicylic acid.
  • Preferred ion-exchange resins (hereinafter, "ion-exchanger") useful herein are water-insoluble resins and consist of a pharmacologically inert organic or inorganic matrix containing covalently bound functional groups that are ionic or capable of being ionized under the appropriate pH conditions.
  • the organic matrix may be synthetic (e.g., polymers or copolymers of acrylic acid, methacrylic acid, sulfonated styrene, sulfonated divinylbenzene), or partially synthetic (e.g., modified cellulose and dextrans).
  • synthetic e.g., polymers or copolymers of acrylic acid, methacrylic acid, sulfonated styrene, sulfonated divinylbenzene
  • partially synthetic e.g., modified cellulose and dextrans
  • the inorganic matrix can also be, e.g., silica gel modified by the addition of ionic groups.
  • the covalently bound ionic groups may be strongly acidic (e.g., sulfonic acid), weakly acidic (e.g., carboxylic acid), strongly basic (e.g., quaternary ammonium), weakly basic (e.g., primary amine), or a combination of acidic and basic groups.
  • ion-exchangers suitable for use in ion-exchange chromatography and for such applications as deionization of water are suitable for use in the compositions of the invention.
  • the particle size of the ion-exchangers is from about 40 microns to about 150 microns. Particle sizes substantially below the lower limit tend to be difficult to handle in all steps of the processing. Particle sizes substantially above the upper limit (e.g., commercially available ion-exchange resins having a spherical shape and diameters up to about 1000 microns) tend to be gritty in solid dosage forms and have a greater tendency to fracture when subjected to drying-hydrating cycles. Binding of drug ingredients and resins can be accomplished by any of the methods known in the art, the selection depending upon the drug ingredient and the ion-exchanger making up the desired drug resin complex. The concentration of the drug ingredient and the resin can be also selected depending upon the characteristic of the resultant drug resin complex necessary to meet the requirement of the therapy.
  • the drug resin complex useful herein can be uncoated or coated.
  • the coating material comprises water permeable diffusion components.
  • the drug active e.g., drug resin complex
  • the drug active is uncoated.
  • the drug resin complex preferably has an uncoated particle size of from about 10 microns to about 150 microns. In coated drug active embodiments, such a size range will increase, commensurate with the thickness of the coating. It is believed a higher particle size of drug resin complex may lead to an unacceptable gritty mouthfeel when the tablet is converted into the paste form in the mouth. The lower particle size tends to provide manufacturing loss and result in difficulty of handling during processing.
  • the drug active useful herein is present at a level of from about 0.5 to about 16.0 %, preferably from about 1.0 to about 12.0%. These levels of drug resin complex without coating are up to 6 times compared to those included in the conventional tablets.
  • the composition of the present invention also includes a thickening agent.
  • thickening agent refers to a material which provides a desirable consistency when contacted with saliva and/or water in the mouth.
  • Such thickening agents in the composition have characteristics such as wetting quickly and absorbing fluid when contacted with water and/or saliva, thereby swelling and converting into a paste. It is believed that water is absorbed into the structure of the composition maintaining cohesiveness of the composition structure. When more and more water enters the composition structure, more swelling takes place and a paste is formed.
  • Nonlimiting examples of thickening agents useful herein include: pregelatinized starch; gums such as agars, locust bean gums, guar gums, and tara gums; carrageenan; alginate; xanthan; dextran; and cellulose derivatives such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose.
  • Natural gums such as gum karaya, gum arabic, and gum tragacanth can also be used.
  • Synthetic silicates such as colloidal magnesium aluminum silicate or finely divided silica can be used as part of the thickening agent to further improve texture.
  • the thickening agent is preferably present from about 0.2% to about 5.5% by weight of the composition.
  • the composition of the present invention also includes a sugar agent.
  • sugar agent refers to a material which is used to enhance salivation and help in dissolution of the composition.
  • the sugar agent presents in the composition can provide sweetness to the formulation, and a desirable dissolution property to the composition as well as aid in the processing of the composition into tablet form.
  • the sugar agent is believed to keep the individual particles of the thickening agent separated and prevent their lumping when contacted with saliva and/or water.
  • the sugar agent useful herein is a sugar, sugar alcohol, or mixture thereof.
  • sugars useful herein include lactose, glucose, maltodextrins, and sucrose.
  • Sugar alcohols useful herein include sorbitol, xylitol, mannitol and maltitol.
  • the total amount of sugar agent is selected depending upon its compatibility with the other ingredients, especially drug actives, and the desired characteristic of the composition such as dissolution and mouthfeel, e.g., bitterness and grittiness of the tablet.
  • the sugar agent is present at an effective level, preferably at a level of from about 20% to about 80%, more preferably from about 20% to about 65% by weight.
  • the sugar agent of the present invention is a combination of sugar and sugar alcohol, more preferably the ratio of sugar of such combination is lower than the ratio of sugar alcohol.
  • a preferred combination is sucrose (sugar) with a higher ratio of mannitol (sugar alcohol). It is believed the combination of sugar and sugar alcohol as the sugar agent improves the pleasant dissolution provided by the combination of the sugar agent with thickening agent. Inclusion of mannitol slows the dissolution speed of the composition as compared to inclusion of sugar only. Without being bound by theory, it is believed that dissolution of a sugar agent having a faster dissolving speed may cause the formation of a thick film around the individual particles of thickening agents, undissolved sugar agents, and other particles included in the composition. Such a thick film tends to prevent further penetration of water into the composition structures and particles which have not dissolved yet; thereby preventing complete and/or even dissolution of the composition as a whole.
  • the composition includes from about 1.0 to about 50% of sugar and from about 20 to about 80% of sugar alcohol by weight of the composition.
  • the sugar agent may further include a binding agent.
  • a binding agent such as mannitol
  • Inclusion of the binding agent is particularly useful when a sugar agent, such as mannitol, may have a limited ability to bind the components used for the composition. It is believed that insufficiencies in binding ability tend to cause tablets to break off, e.g., into two pieces along the length of the tablet during the manufacturing process. This splitting of the tablet is commonly referred to as "capping.”
  • the levels and types of binding agent are selected depending upon the character of the carriers, compatibility with other components, and desired characteristic of the final product.
  • sugar agent of the present invention may also have properties as a binding agent for making tablets.
  • Most of the sugar agents herein, preferably sugar, may be useful for providing improved binding properties of the composition in tablet form to prevent the tablet from breaking into two pieces.
  • binding agents other than the previously described sugar agents, include starches such as starch paste and pregelatinized starch; polyvinylpyrrolidone; cellulose derivatives; gelatin; gums; and mixtures thereof.
  • the binding agent and the tableting carrier may be made of the same material.
  • the binding agent and the sugar agent may be altogether different.
  • the binding agent is present in an effective amount, preferably from about 0.1% to about 5% by weight, more preferably from about 0.5% to about 3%.
  • the composition of the present invention can further include a water insoluble diluent.
  • water insoluble diluent means a material which improves the disintegration or dispersion property of the tablet composition. Without being bound by theory, it is believed that the water insoluble diluent tends to provide a desired porosity to the composition. Such porosity is believed to provide channels for water into the tablet structure, thereby allowing penetration of, and more exposure of the composition surface area to, the water.
  • the water insoluble diluent useful herein is any material which is insoluble in water which improves the dissolution of the composition, versus a composition that does not contain the material.
  • the water insoluble diluent useful herein includes, but is not limited to, calcium carbonate, calcium phosphate, and the like.
  • the water insoluble diluent is present at an effective level, preferably at a level of from about 0.5% to about 70% of the tablet composition.
  • the composition of the present invention can further include a tableting carrier.
  • tabletteing carrier means one or more compatible solid or liquid substances, preferably in solid form, which are suitable for oral administration to a human and commonly used for making tablets.
  • the tableting carrier must be of sufficiently high purity and sufficiently low toxicity to render the tablet suitable for administration to human beings.
  • useful tableting carriers include the water insoluble diluent, a tableting aid, a coloring agent, a flavoring agent, the granulating fluid, and mixtures thereof.
  • the tableting carrier is present from about 10 to about 80%, more preferably from about 30 to about 80% by weight.
  • tabletteing aid refers to an ingredient that is added in small quantities to the composition to provide flowability during manufacturing, to reduce friction, and/or to ease removal of the tablets from the tableting machine.
  • the tableting aids useful herein include, for example, magnesium stearate, stearic acid, aerosol, talc, and mixtures thereof.
  • the tableting aid is present in an amount sufficient to prevent the tablet from breaking into two pieces, preferably from about 2% to about 8%, by weight.
  • the tablet composition of the present invention may further include a coloring agent.
  • the coloring agent is added with the granulating fluid to facilitate uniform distribution and mixing
  • the coloring agent is present at an effective level, preferably from about 10ppm to about 500ppm, more preferably from about 20ppm to about 250ppm by weight 3.
  • Flavoring agents may also be added to the tablet composition of the present invention.
  • flavoring agents useful herein include oil of peppermint, oil of sassafras, clove bud oil, peppermint, menthol, anethole, thymol, methyl salicylate, eucalyptol, cassia, 1-menthyl acetate, sage, eugenol, parsley oil, oxanone, oil of wintergreen, alpha-irisone, oil of spearmint, marjoram, lemon, orange, propenyl guaethol, cinnamon, and mixtures thereof.
  • Flavoring agents are generally used in the tablet composition at levels of from about 0.01% to about 5% by weight.
  • the tablet composition in accordance with the present invention may further, optionally, include other known compounds having the capability to enhance substantivity of a sweetener, if desired. These compounds is added to increase the overall sweetness impact.
  • Such compounds include, but are not limited to, saccharine, aspartame, acesulfame K, and glycyrrhizin.
  • composition of the present invention in tablet form can be produced by any method useful for forming conventional tablets known in the art.
  • These conventional methods include granulating methods: either wet or dry granulating method, preferably wet granulating.
  • granulating methods either wet or dry granulating method, preferably wet granulating.
  • the ingredients e.g., drug resin complexes, thickening agents, pharmaceutical acceptable carriers, flavors, coloring agents, and the like
  • the wet granulation method is widely used and usually produces the most satisfactory results in tablets. See, for example, E.J. de Jong; "The preparation of microgranulates, an improved tableting technique," Pharmaceutical Weekblad, 104(23), pages 469-474, 1969 and E.J. de Jong, U.S. Patent 3,266,992.
  • Direct compression may also be chosen for the present composition, as long as producing non-gritty tablets does not cause capping. See, for example, Blaaze, T. Palermo, et al., U.S. Patent 3,384,546.
  • a method for making a composition in tablets form of the present invention comprises: (1) adding drug actives, sugar agents and any of additional ingredients which are stable in the proceeding process (e.g., coloring agent), if needed, to make granules; (2) passing the granules through #10 mesh; (3) drying the sieved granules through conventional drying techniques; (4) sieving again the dried granules through #14 mesh; (5) mixing the granules of step (4) with a thickening agent and any additional ingredients (e.g., sweetening agent, flavour, tableting aids); and (6) compressing the mixture of step (5) to form tablets by conventional method.
  • additional ingredients e.g., coloring agent
  • the tablet having Example 2 formulation is made by the method described in "Method for making tablets" section, except the drug actives are added at step 5 during mixing of the granules, rather than at step 1.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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Abstract

La présente invention concerne une composition de comprimé renfermant: (a) un principe actif; (b) un agent épaississant; et (c) un produit sucrant, la composition se présentant sous la forme solide et le rapport entre l'agent épaississant et le produit sucrant étant tel que la composition se transforme en pâte lorsqu'elle entre en contact avec la salive.
PCT/US1997/024122 1997-12-29 1997-12-29 Composition de comprime WO1999033445A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP97954647A EP1041965A1 (fr) 1997-12-29 1997-12-29 Composition de comprime
CA002317021A CA2317021A1 (fr) 1997-12-29 1997-12-29 Composition de comprime
AU59046/98A AU5904698A (en) 1997-12-29 1997-12-29 Tablet composition
PCT/US1997/024122 WO1999033445A1 (fr) 1997-12-29 1997-12-29 Composition de comprime
JP11514272A JP2000516263A (ja) 1997-12-29 1997-12-29 錠剤組成物

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1997/024122 WO1999033445A1 (fr) 1997-12-29 1997-12-29 Composition de comprime

Publications (1)

Publication Number Publication Date
WO1999033445A1 true WO1999033445A1 (fr) 1999-07-08

Family

ID=22262396

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/024122 WO1999033445A1 (fr) 1997-12-29 1997-12-29 Composition de comprime

Country Status (5)

Country Link
EP (1) EP1041965A1 (fr)
JP (1) JP2000516263A (fr)
AU (1) AU5904698A (fr)
CA (1) CA2317021A1 (fr)
WO (1) WO1999033445A1 (fr)

Cited By (5)

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WO2003097016A1 (fr) * 2002-05-20 2003-11-27 John Kohnke Systeme d'administration d'agent
WO2006067593A1 (fr) * 2004-12-23 2006-06-29 Mcneil-Ppc, Inc. Compositions pharmaceutiques a dissolution orale contenant des agents a effet sensoriel
AU2003229357B2 (en) * 2002-05-20 2008-05-15 John Kohnke Agent delivery system
WO2010132431A1 (fr) 2009-05-11 2010-11-18 Jrs Pharma Gmbh+Co.Kg Excipient se désintégrant par voie orale
EP3723722B1 (fr) 2017-12-13 2022-11-16 Roquette Freres Système épaississant et stabilisant d'origine naturelle convenant notamment à la préparation de produits cosmétiques

Families Citing this family (5)

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HRP20020924A2 (en) 2001-11-23 2003-10-31 Glaxo Group Ltd Pharmaceutical composition
JP4845353B2 (ja) * 2004-06-29 2011-12-28 田辺三菱製薬株式会社 陰イオン交換樹脂を含む医薬組成物
US20090306154A1 (en) * 2006-07-13 2009-12-10 Symrise Gmbh & Co., Kg Synergistic anti-microbial mixtures of tropolone (derivatives) and selected compounds
WO2010038695A1 (fr) * 2008-09-30 2010-04-08 大洋薬品工業株式会社 Préparation moulée par compression et son procédé de production
JP7390695B2 (ja) * 2017-02-03 2023-12-04 株式会社東洋新薬 錠剤及び錠剤の製造方法

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EP0487774A1 (fr) * 1990-11-29 1992-06-03 Wei Ming Pharmaceutical Mfg. Co. Ltd. Auxiliaire de compression directe
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WO1994012180A1 (fr) * 1992-11-27 1994-06-09 Smithkline Beecham Plc Granules de cimetidine enrobes d'huile vegetale partiellement hydrogenee
US5320848A (en) * 1991-05-28 1994-06-14 Affinity Biotech, Inc. Chewable drug-delivery composition
WO1994014422A1 (fr) * 1992-12-24 1994-07-07 Oregon Freeze Dry Comprime ameliore a desagregation rapide
US5633005A (en) * 1991-12-05 1997-05-27 Bolder Arzneimittel Gmbh Dimeticon pastilles
US5686107A (en) * 1995-01-30 1997-11-11 Fmc Corporation Chewable pharmaceutical tablets

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EP0435684A1 (fr) * 1989-12-28 1991-07-03 R.P. Scherer Corporation Formes de dosage lyophilisées et procédés de leur préparation
US5188825A (en) * 1989-12-28 1993-02-23 Iles Martin C Freeze-dried dosage forms and methods for preparing the same
EP0471967A1 (fr) * 1990-07-19 1992-02-26 MERCK PATENT GmbH Comprimé à mâcher à base de sucralfate
EP0487774A1 (fr) * 1990-11-29 1992-06-03 Wei Ming Pharmaceutical Mfg. Co. Ltd. Auxiliaire de compression directe
EP0492235A1 (fr) * 1990-12-20 1992-07-01 Basf Corporation Composition à faible taux d'humidité à base de cholestyramine
US5262167A (en) * 1990-12-20 1993-11-16 Basf Corporation Edible, non-baked low moisture cholestyramine composition
US5320848A (en) * 1991-05-28 1994-06-14 Affinity Biotech, Inc. Chewable drug-delivery composition
US5633005A (en) * 1991-12-05 1997-05-27 Bolder Arzneimittel Gmbh Dimeticon pastilles
WO1994012180A1 (fr) * 1992-11-27 1994-06-09 Smithkline Beecham Plc Granules de cimetidine enrobes d'huile vegetale partiellement hydrogenee
US5597844A (en) * 1992-11-27 1997-01-28 Chauhan; Sushil Cimetidine granules coated with a partially hydrogenated vegetable oil
WO1994014422A1 (fr) * 1992-12-24 1994-07-07 Oregon Freeze Dry Comprime ameliore a desagregation rapide
US5686107A (en) * 1995-01-30 1997-11-11 Fmc Corporation Chewable pharmaceutical tablets

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003097016A1 (fr) * 2002-05-20 2003-11-27 John Kohnke Systeme d'administration d'agent
GB2406518A (en) * 2002-05-20 2005-04-06 John Kohnke Agent delivery system
GB2406518B (en) * 2002-05-20 2006-02-08 John Kohnke Agent delivery system
AU2003229357B2 (en) * 2002-05-20 2008-05-15 John Kohnke Agent delivery system
US8802141B2 (en) 2002-05-20 2014-08-12 John Kohnke Agent delivery system
WO2006067593A1 (fr) * 2004-12-23 2006-06-29 Mcneil-Ppc, Inc. Compositions pharmaceutiques a dissolution orale contenant des agents a effet sensoriel
WO2010132431A1 (fr) 2009-05-11 2010-11-18 Jrs Pharma Gmbh+Co.Kg Excipient se désintégrant par voie orale
EP2429586A1 (fr) * 2009-05-11 2012-03-21 Jrs Pharma GmbH+Co.kG Excipient se désintégrant par voie orale
EP2429586A4 (fr) * 2009-05-11 2013-08-28 Jrs Pharma Gmbh & Co Kg Excipient se désintégrant par voie orale
EP3723722B1 (fr) 2017-12-13 2022-11-16 Roquette Freres Système épaississant et stabilisant d'origine naturelle convenant notamment à la préparation de produits cosmétiques

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JP2000516263A (ja) 2000-12-05
EP1041965A1 (fr) 2000-10-11
CA2317021A1 (fr) 1999-07-08
AU5904698A (en) 1999-07-19

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