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WO1995008988A1 - Comprime contenant une masse de base contenant le cas echeant des principes actifs et des microparticules contenant des principes actifs - Google Patents

Comprime contenant une masse de base contenant le cas echeant des principes actifs et des microparticules contenant des principes actifs Download PDF

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Publication number
WO1995008988A1
WO1995008988A1 PCT/EP1994/003166 EP9403166W WO9508988A1 WO 1995008988 A1 WO1995008988 A1 WO 1995008988A1 EP 9403166 W EP9403166 W EP 9403166W WO 9508988 A1 WO9508988 A1 WO 9508988A1
Authority
WO
WIPO (PCT)
Prior art keywords
microparticles
tablet according
tablet
active ingredient
eudragit
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
Application number
PCT/EP1994/003166
Other languages
German (de)
English (en)
Inventor
Werner Korsatko
Brigitte Korsatko
Wolfram Tritthart
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Priority to AU78088/94A priority Critical patent/AU7808894A/en
Priority to EP94928795A priority patent/EP0715515A1/fr
Publication of WO1995008988A1 publication Critical patent/WO1995008988A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

Definitions

  • the invention relates to a novel tablet for use as a chewing and / or disintegrating tablet.
  • the active ingredient is usually incorporated into matrix tablets, film-coated tablets or retard pellets, the pellets then being filled into capsules or compressed into swallowing tablets.
  • the size of the tablets or capsules is naturally limited to a weight of approximately 0.6 g. Even tablets or capsules with this weight have considerable difficulties in swallowing. Both tablets and capsules cannot be bitten before swallowing, as this would destroy the pellets and matrices and the sustained-release effect would be lost.
  • the invention is therefore based on the object of providing a novel chewing and / or disintegrating tablet which enables a delayed release of active substance while avoiding the disadvantages of the prior art.
  • this object is achieved in that active ingredient-containing microparticles with retarding properties are present in a conventional base composition which is suitable for biting and / or disintegrating in liquid, which, because of their elasticity and strength, do not destroy when the tablet is bitten and / or disintegrates become.
  • the base composition has at least one additional active ingredient, which, in the event that the microparticles contain sodium fluorophosphate or sodium fluoride, contains at least one calcium salt or a calcium complex.
  • the invention further proposes that the base mass contains the same active ingredient (s) as the microparticles.
  • the amount of active ingredient in the base mass can preferably be set so that it acts as an initial dose and the amount in the microparticles so that it acts as a maintenance dose.
  • the microparticles consist of a retarding, elastic, active substance-containing matrix and a retarding and likewise elastic shell.
  • the elastic matrix can be made from an Eudragit derivative or a composition of various Eudragit derivatives, cellulose derivatives such as methyl cellulose, hydroxyethyl cellulose or hydroxypropyl cellulose or other conventional retarding adjuvants high proportion of plasticizing components, while the shell is preferably made of polyacrylates, such as ⁇ ⁇
  • Eudragit or Eudragit compositions or of cellulose derivatives, such as ethyl cellulose, cellulose acetate phthalate or hydroxypropyl ethyl cellulose phthalate, optionally with the addition of plasticizing auxiliaries.
  • the invention relates to a tablet with microparticles with a content of 0.3 to 3.0 mm, preferably 0.3 to 1.0 mm.
  • the invention also relates to tablets containing sodium fluorophosphate or sodium fluoride in the microparticles and optionally at least one calcium salt or calcium complex in the base material, for the prevention or therapy of osteoporosis.
  • the invention relates to a tablet containing naftidrofuryl salt e.g. Naftidrofuryl hydrogen oxalate in the microparticles, for blood circulation and / or vasodilation.
  • naftidrofuryl salt e.g. Naftidrofuryl hydrogen oxalate in the microparticles
  • the invention also relates to a tablet with a content of diclofenac or its salt in the microparticles, as an anti-inflammatory and / or anti-rheumatic.
  • the invention relates to a tablet containing cimetidine or ranitidine or their salts in the microparticles as an H 2 blocker.
  • the invention also relates to a tablet containing pentoxyfylline in the microparticles as a vasodilatane. Furthermore, the invention relates to a tablet containing loratadine as an antiallergic.
  • the invention also relates to a tablet containing ⁇ -blockers, such as propanolol and atenolol, or ⁇ -blockers, such as clonidine, or their salts in the microparticles, as an antihypertensive.
  • ⁇ -blockers such as propanolol and atenolol
  • ⁇ -blockers such as clonidine
  • the invention relates to a tablet containing furosemide or hydrochlorothiazide in the microparticles as a diuretic.
  • the measures according to the invention provide for the first time a chewing and / or disintegrating tablet in which the active ingredient or combination of active ingredients is released in a retarded manner.
  • a particular advantage here is that the active ingredient contained in the microparticles can be metered in such a way that it was not possible when incorporating them into previously used oral retardation systems.
  • the active ingredient or combination of active ingredients is present exclusively in the microparticles.
  • Particularly high-dose active ingredients which, according to the state of knowledge, could not be applied or could only be applied in a retarded form to a limited extent, can thus be taken in the form of a chewing tablet and / or disintegration tablet.
  • the incorporation of the active ingredient or combination of active ingredients into the microparticles designed according to the invention does not adversely affect the retarding properties when the tablet is chewed and / or disintegrated, since the microparticles are not destroyed due to their elasticity and strength when they are chewed and / or disintegrated.
  • Depending on the structure of the retard Systems of the microparticles result in a delayed release at a later point in time, for example in the gastrointestinal tract after passage through the stomach.
  • the active ingredient or combination of active ingredients is contained both in the microparticles and in the base material, the amounts then being able to be adjusted so that the active ingredient is contained in the basic mass, which is released immediately, acts as an initial dose, while the amount of active ingredient in the microparticles, which is released only after a delay, acts as a maintenance dose.
  • the elastic retard matrix is made of cellulose
  • compositions built up The terms Avicel, Methocel and Eudragit used in this context are registered trademarks.
  • tablets are also provided according to the invention in which, as an initial dose, part of the active ingredient is present in the base material and another part, as a maintenance dose, is present in the microparticles.
  • calcium salts can be provided in the base composition in order to provide a combination preparation for the treatment of osteoporosis.
  • MFP in microparticles 50 mg MFP MFP in basic mass 50 mg MFP calcium salts 500 mg approx
  • MFP in microparticles 140 mg MFP MFP in basic mass 60 mg MFP calcium salts 500 mg approx
  • tablets constructed according to the invention with the active ingredient sodium fluoride can also be used in the microparticles, an example of a possible composition being given in Table 2 below.
  • composition of a tablet according to the invention contains naftidrofuryl hydrogen oxalate as an active ingredient, which promotes blood circulation and vasodilator.
  • ® is embedded, is based on an Eudragit composition, while the tablet base (as shown) can have different compositions.
  • Table 4 shows a tablet according to the invention in which the microparticles contain the active ingredient diclofenac, which has an anti-inflammatory and anti-rheumatic effect.
  • the elastic matrix in which this active ingredient is embedded in the microparticles also consists of the cellulose derivative Avicel.
  • FIG. 2 shows the in vitro liberation of the active ingredient diclofenac from the tablets described above.
  • game 6 shows the in vitro liberation of the active ingredient diclofenac from the tablets described above.
  • the chewing tablets described in Examples 1 to 5 above can be used as disintegration tablets without changing the composition.
  • Corresponding investigations have shown that when these tablets are placed in a glass filled with water (e.g. 50 ml), they largely disintegrate there within a period of about 3 minutes to form an ingestible suspension.
  • the structure of the tablets according to the invention therefore not only provides a chewing tablet, but also a disintegrating tablet with delayed release of active ingredient, which avoids the disadvantages of conventional swallowing tablets described at the outset.
  • Vasodilatants e.g.
  • ⁇ -blockers such as propranolol, atenolol + magnesium salts
  • ⁇ -blockers such as clonidine + magnesium salts + potassium salts

Landscapes

  • 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)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

Un comprimé à mâcher et/ou à dissoudre contient dans une masse usuelle de base propre à mâcher et/ou qui se dissout dans un liquide des microparticules à effet retardateur qui contiennent le principe actif et qui, compte tenue de leur élasticité et de leur solidité, ne sont pas détruites lorsque le comprimé est mâché et/ou se dissout.
PCT/EP1994/003166 1993-09-29 1994-09-22 Comprime contenant une masse de base contenant le cas echeant des principes actifs et des microparticules contenant des principes actifs Ceased WO1995008988A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU78088/94A AU7808894A (en) 1993-09-29 1994-09-22 Tablet containing a basic material possibly containing active substances and active substance containing microparticles
EP94928795A EP0715515A1 (fr) 1993-09-29 1994-09-22 Comprime contenant une masse de base contenant le cas echeant des principes actifs et des microparticules contenant des principes actifs

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19934333190 DE4333190C2 (de) 1993-09-29 1993-09-29 Zerbeißtablette mit verzögerter Wirkstoff-Freisetzung
DEP4333190.4 1993-09-29

Publications (1)

Publication Number Publication Date
WO1995008988A1 true WO1995008988A1 (fr) 1995-04-06

Family

ID=6498970

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1994/003166 Ceased WO1995008988A1 (fr) 1993-09-29 1994-09-22 Comprime contenant une masse de base contenant le cas echeant des principes actifs et des microparticules contenant des principes actifs

Country Status (4)

Country Link
EP (1) EP0715515A1 (fr)
AU (1) AU7808894A (fr)
DE (1) DE4333190C2 (fr)
WO (1) WO1995008988A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19648576A1 (de) * 1996-11-23 1998-06-04 Karsten Dr Cremer Lutschtablette zur modifizierten Freisetzung von Wirkstoffen im Gastrointestinaltrakt
WO2005074885A1 (fr) * 2004-02-03 2005-08-18 Philippe Perovitch Procede de diffusion de molecules insolubles en milieu aqueux et composition mettant en oeuvre ce procede
US7125562B2 (en) 1997-08-22 2006-10-24 Smithkline Beecham Corporation Rapidly disintegrating methylcellulose tablets
US7132114B2 (en) 1997-08-22 2006-11-07 Smithkline Beecham Corporation Rapidly disintegrating methylcellulose tablets

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2251623C (fr) 1996-05-13 2006-12-19 Novartis Consumer Health S.A. Systeme de liberation gingivo-jugal

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2047096A (en) * 1979-04-09 1980-11-26 Sanofi Sa Naftidrofuryl composition for immediate and delayed release
EP0153104A2 (fr) * 1984-02-10 1985-08-28 Benzon Pharma A/S Dose à base d'unités multiples enrobées par une couche de diffusion
EP0207405A2 (fr) * 1982-07-27 1987-01-07 Mylan Pharmaceuticals, Inc. Procédé pour la préparation d'une composition pharmaceutique combinée sous la forme d'une dose unitaire hétérogène de granulés possédant une biodisponibilité accrue
WO1987002240A1 (fr) * 1985-10-11 1987-04-23 Aktiebolaget Hässle Nouvelle preparation medicamenteuse a liberation controlee de l'ingredient actif, son procede de fabrication et utilisation de la nouvelle preparation
EP0294933A2 (fr) * 1987-05-08 1988-12-14 Smith Kline & French Laboratories Limited Compositions pharmaceutiques
EP0355247A2 (fr) * 1988-08-22 1990-02-28 Ss Pharmaceutical Co., Ltd. Préparations moulées par compression
EP0381219A2 (fr) * 1989-02-02 1990-08-08 Warner-Lambert Company Composition à base de gemfibrozil à libération modifiée
WO1991017743A1 (fr) * 1990-05-17 1991-11-28 Europharmaceuticals S.A. Compositions pharmaceutiques du type a liberation prolongee destinees a l'administration par voie orale et leur procede de preparation
EP0503425A1 (fr) * 1991-03-14 1992-09-16 MERCK PATENT GmbH Pellets contenant du monofluorphosphate de sodium
FR2679451A1 (fr) * 1991-07-22 1993-01-29 Prographarm Laboratoires Comprime multiparticulaire a delitement rapide.
EP0525388A1 (fr) * 1991-07-01 1993-02-03 Gerhard Dr. Gergely Comprimé à sucer ou à mâcher

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4861590A (en) * 1986-09-25 1989-08-29 Colgate-Palmolive Company Sustained release fluoride and calcium composition
DE4236090C1 (de) * 1992-10-26 1994-01-05 Asta Medica Arzneimittel Pharmazeutische Zubereitung für die Fluoridionen-Versorgung

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2047096A (en) * 1979-04-09 1980-11-26 Sanofi Sa Naftidrofuryl composition for immediate and delayed release
EP0207405A2 (fr) * 1982-07-27 1987-01-07 Mylan Pharmaceuticals, Inc. Procédé pour la préparation d'une composition pharmaceutique combinée sous la forme d'une dose unitaire hétérogène de granulés possédant une biodisponibilité accrue
EP0153104A2 (fr) * 1984-02-10 1985-08-28 Benzon Pharma A/S Dose à base d'unités multiples enrobées par une couche de diffusion
WO1987002240A1 (fr) * 1985-10-11 1987-04-23 Aktiebolaget Hässle Nouvelle preparation medicamenteuse a liberation controlee de l'ingredient actif, son procede de fabrication et utilisation de la nouvelle preparation
EP0294933A2 (fr) * 1987-05-08 1988-12-14 Smith Kline & French Laboratories Limited Compositions pharmaceutiques
EP0355247A2 (fr) * 1988-08-22 1990-02-28 Ss Pharmaceutical Co., Ltd. Préparations moulées par compression
EP0381219A2 (fr) * 1989-02-02 1990-08-08 Warner-Lambert Company Composition à base de gemfibrozil à libération modifiée
WO1991017743A1 (fr) * 1990-05-17 1991-11-28 Europharmaceuticals S.A. Compositions pharmaceutiques du type a liberation prolongee destinees a l'administration par voie orale et leur procede de preparation
EP0503425A1 (fr) * 1991-03-14 1992-09-16 MERCK PATENT GmbH Pellets contenant du monofluorphosphate de sodium
EP0525388A1 (fr) * 1991-07-01 1993-02-03 Gerhard Dr. Gergely Comprimé à sucer ou à mâcher
FR2679451A1 (fr) * 1991-07-22 1993-01-29 Prographarm Laboratoires Comprime multiparticulaire a delitement rapide.
WO1993001805A1 (fr) * 1991-07-22 1993-02-04 Laboratoires Prographarm Comprime multiparticulaire a delitement rapide

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19648576A1 (de) * 1996-11-23 1998-06-04 Karsten Dr Cremer Lutschtablette zur modifizierten Freisetzung von Wirkstoffen im Gastrointestinaltrakt
DE19648576C2 (de) * 1996-11-23 1999-08-12 Lohmann Therapie Syst Lts Lutschtablette zur modifizierten Freisetzung von Wirkstoffen im Gastrointestinaltrakt
US7125562B2 (en) 1997-08-22 2006-10-24 Smithkline Beecham Corporation Rapidly disintegrating methylcellulose tablets
US7132114B2 (en) 1997-08-22 2006-11-07 Smithkline Beecham Corporation Rapidly disintegrating methylcellulose tablets
WO2005074885A1 (fr) * 2004-02-03 2005-08-18 Philippe Perovitch Procede de diffusion de molecules insolubles en milieu aqueux et composition mettant en oeuvre ce procede
US8846083B2 (en) 2004-02-03 2014-09-30 Philippe Perovitch Method for the diffusion of molecules which are insoluble in an aqueous medium and composition using said method

Also Published As

Publication number Publication date
DE4333190A1 (de) 1995-03-30
AU7808894A (en) 1995-04-18
EP0715515A1 (fr) 1996-06-12
DE4333190C2 (de) 1996-05-30

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