WO1996004892A1 - Novel cimetidine-containing compositions and combinations derived therefrom - Google Patents

Novel cimetidine-containing compositions and combinations derived therefrom Download PDF

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Publication number
WO1996004892A1
WO1996004892A1 PCT/FR1995/001080 FR9501080W WO9604892A1 WO 1996004892 A1 WO1996004892 A1 WO 1996004892A1 FR 9501080 W FR9501080 W FR 9501080W WO 9604892 A1 WO9604892 A1 WO 9604892A1
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Prior art keywords
cimetidine
composition
excipient
release
weight
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PCT/FR1995/001080
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French (fr)
Inventor
Pawan Seth
André Stamm
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Pharma Pass
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Priority to AU31800/95A priority Critical patent/AU3180095A/en
Publication of WO1996004892A1 publication Critical patent/WO1996004892A1/en

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    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the subject of the present invention is new compositions containing cimetidine, and in particular new compositions for sustained release of cimetidine.
  • the present invention also relates to a combination of two cimetidine compositions, one with immediate release and the other with sustained release.
  • Cimetidine is a histamine H2 receptor antagonist that inhibits the secretion of gastric acid stimulated by the histamine and reduces the total flow of pepsin.
  • cimetidine has been formulated in an immediate release form.
  • immediate release dosage forms tend to cause reflex hyperacidity in the stomach.
  • the known sustained-release dosage forms have a certain number of drawbacks. It is difficult to prepare a dosage form concentrated in active principle, because in order to have a correct prolonged release effect, the dosage form must contain a sufficient quantity of excipients fulfilling the delayed release function; this has the consequence of leading to a dosage form of too large a dimension.
  • the present invention overcomes the drawbacks of the prior art.
  • the present invention provides a composition comprising, by weight:
  • excipient means any material or mixture of materials which is inert with respect to cimetidine, and pharmaceutically acceptable.
  • composition exhibits a prolonged release effect, while containing a high proportion of the active principle which is cimetidine.
  • cimetidine as used in the invention, also denotes its pharmaceutically acceptable derivatives; the percentages by weight will however be calculated on the basis of the free cimetidine form.
  • the weight percentages in the composition are calculated on the basis of the final composition.
  • composition according to the invention comprises, by weight:
  • composition according to the invention comprises, by weight:
  • any material, preferably polymer, known in the art and which leads to a gel in the presence of water, can be used.
  • the viscosity of this agent is at least 3 mPa.s. (the viscosity is measured for a solution at 1% by weight, at 23 ° C., using a viscometer with a rotating mobile).
  • examples of such agents are hydroxypropy imethylcellulose, ethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polyethyleneoxide, synthetic and natural polymers such as gelatin, gums, algmate, carrageenans, etc.
  • binder any binder material, preferably polymer, conventionally used in the art can be used. Examples of such agents are cellulose derivatives, polyvinylpyrrolidone, polyvinyl alcohol, gelatin, gums, polyethylene oxide, etc.
  • the gel-forming agent is also a binder.
  • any material preferably polymer, can be used.
  • examples of such agents are hydroxypropylmethylcellulose, ethylcellulose, poly ⁇ ethyleneoxide
  • the gel-forming agent and binder has a viscosity of at least 3 mPa.s.
  • the present invention remedies this deficiency in the prior art, and provides an association comprising; -
  • the immediate-release composition comprises, by weight:
  • said immediate-release composition comprises, by weight:
  • said immediate release cimetidme composition contains from 50 to 400 mg, preferably from 100 to 300 mg and advantageously about 200 mg of cimetidme; and said sustained release cimetidme composition contains from 200 to 600 mg, preferably from 300 to 500 mg and preferably about 400 mg of cimetidme.
  • the combination according to the invention is in the form of a capsule containing the said cimetidine compositions in the form of tablets.
  • This unit dosage form is entirely suitable for oral administration, and offers, from its ingestion, a therapeutic effect, which is extended over time over a few hours.
  • any suitable capsule conventionally used in the art can be used.
  • examples of such capsules are the capsules, for example hard gelatin, commercially available from Capsugel, Eli-lilly, Scherer.
  • a subject of the invention is also the composition according to the invention, for its use as a medicament for the treatment of gastric acidity.
  • Another subject of the invention is the association according to the invention, for its use as a medicament for the treatment of gastric acidity.
  • Another advantage of the invention is that the active principle, cimetidine, is present in a majority amount relative to the excipient, which allows the realization of dosage forms of very reduced volume.
  • the dosage forms which the invention provides, and in particular the combination according to the invention, of reduced volume, but containing a high amount of active principle are particularly suitable for administration by the oral route and are perfectly accepted by patients.
  • FIG. 1 is a section of the capsule according to the invention
  • FIG. 2 represents the in vitro dissolution of a drug combination according to the invention as a function of time
  • Figures 3a and 3b show, respectively, the average pH of the stomach and the average plasma concentration of cimetidine as a function of time.
  • the capsule (1) contains a tablet (2) corresponding to a rapid-release composition and the tablet (3) corresponding to a prolonged-release composition.
  • Example 1 illustrate the invention without, however, limiting its scope.
  • Two tablets are conventionally prepared, which are intended to be placed in a capsule, for example a hard gelatin capsule:
  • Methocel E15LV hydroxypropyl methylcellulose 6
  • composition in mg of the immediate-release tablet Cimetidine 200 Pharmacoat 606 (hydroxypropyl methylcellulose) 6 Sodium carboxymethylcellulose 10
  • Cimetidine 400 Polyox 301 (polyethylene oxide) 30 Magnesium stearate 4
  • FIG. 2 gives the graph of the percentage of active principle released as a function of time.

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

Abstract

The object of this invention is a composition containing, by weight, (a) 50-99 % of cimetidine and (b) 1-50 % of a carrier which contains at least a gel forming agent, a binding agent, and a lubricating agent. Also disclosed is a combination containing said composition, and uses thereof as medicament.

Description

NOUVELLES COMPOSITIONS CONTENANT DE LA CIMETIDINE ET ASSOCIATIONS EN DÉRIVANT NOVEL COMPOSITIONS CONTAINING CIMETIDINE AND DERIVATIVE ASSOCIATIONS THEREOF
La présente invention a pour objet de nouvelles compositions contenant de la cimetidine, et en particulier de nouvelles compositions à libération prolongée de cimetidine. La présente invention a aussi pour objet une association de deux compositions de cimetidine, l'une à libération immédiate et l'autre à libération prolongée. La cimetidine est un antagoniste des récepteurs H2 à l'histamme qui inhibe la sécrétion d'acide gastrique stimulée par l'histamme et réduit le débit total de pepsine.The subject of the present invention is new compositions containing cimetidine, and in particular new compositions for sustained release of cimetidine. The present invention also relates to a combination of two cimetidine compositions, one with immediate release and the other with sustained release. Cimetidine is a histamine H2 receptor antagonist that inhibits the secretion of gastric acid stimulated by the histamine and reduces the total flow of pepsin.
Jusqu'à présent, la cimetidine était formulée sous une forme à libération immédiate. Une étude réalisée par M.J. Ostro et al., Gastroentenology, 1985, 89, 532 montre que la concentration de principe actif présent dans le sang pendant une période prolongée permet un contrôle de l'acidité gastrique qui est meilleur que celui obtenu par administration de cimetidine à différents intervalles.Until now, cimetidine has been formulated in an immediate release form. A study carried out by MJ Ostro et al., Gastroentenology, 1985, 89, 532 shows that the concentration of active ingredient present in the blood for a prolonged period allows a control of the gastric acidity which is better than that obtained by administration of cimetidine at different intervals.
Par ailleurs, les formes de dosage à libération immédiate tendent à provoquer une hyperacidité réflexe au niveau de l'estomac.In addition, immediate release dosage forms tend to cause reflex hyperacidity in the stomach.
On recherche donc des compositions à effet retard ou présentant une libération prolongée. Or, les formes de dosage connues à libération prolongée présentent un certain nombre d'inconvénients. Il est difficile de préparer une forme de dosage concentrée en principe actif, car pour présenter un effet de libération prolongée correct, la forme de dosage doit renfermer une quantité suffisante d'excipients remplissant la fonction de libération retard; ceci a pour conséquence de conduire a une forme de dosage d'une dimension trop importante La présente invention permet de remédier aux inconvénients de l'art antérieur Ainsi, la présente invention fournit une composition comprenant, en poids :We are therefore looking for compositions with a delayed effect or with sustained release. However, the known sustained-release dosage forms have a certain number of drawbacks. It is difficult to prepare a dosage form concentrated in active principle, because in order to have a correct prolonged release effect, the dosage form must contain a sufficient quantity of excipients fulfilling the delayed release function; this has the consequence of leading to a dosage form of too large a dimension. The present invention overcomes the drawbacks of the prior art. Thus, the present invention provides a composition comprising, by weight:
(a) 50-99% de cimetidine; et (b) 1-50% d'un excipient, ledit excipient contenant au moins un agent formant un gel, un agent liant et un agent lubrifiant.(a) 50-99% cimetidine; and (b) 1-50% of an excipient, said excipient containing at least one gel-forming agent, a binding agent and a lubricating agent.
Par le terme "excipient" tel qu'utilisé dans la présente description, on entend tout matériau ou mélange de matériaux qui soit inerte vis-à-vis de la cimetidine, et pharmaceutiquement acceptable.The term "excipient" as used in the present description means any material or mixture of materials which is inert with respect to cimetidine, and pharmaceutically acceptable.
Cette composition présente un effet de libération prolongée, tout en contenant une proportion élevée du principe actif qui est la cimetidine. Le terme "cimetidine", tel qu'utilisé dans l'invention, désigne aussi ses dérivés pharmaceutiquement acceptables; les pourcentages en poids seront cependant calculés sur la base de la forme cimetidine libre.This composition exhibits a prolonged release effect, while containing a high proportion of the active principle which is cimetidine. The term "cimetidine", as used in the invention, also denotes its pharmaceutically acceptable derivatives; the percentages by weight will however be calculated on the basis of the free cimetidine form.
Les pourcentages en poids dans la composition sont calculés sur la base de la composition finale.The weight percentages in the composition are calculated on the basis of the final composition.
Selon un mode de réalisation, la composition selon l'invention comprend, en poids :According to one embodiment, the composition according to the invention comprises, by weight:
(a) 75-98% de cimetidine; et(a) 75-98% cimetidine; and
(b) 1-25% dudit excipient. Selon un autre mode de réalisation, la composition selon l'invention, comprend, en poids :(b) 1-25% of said excipient. According to another embodiment, the composition according to the invention comprises, by weight:
(a) 85-95% de cimetidine; et(a) 85-95% cimetidine; and
(b) 5-15% dudit excipient.(b) 5-15% of said excipient.
En tant qu'agent formant un gel, on peut utiliser tout matériau, de préférence polymère, connu dans l'art et qui conduit a un gel en présence d'eau. La viscosité de cet agent est d'au moins 3 mPa.s. (la viscosité est mesurée pour une solution à 1% en poids, a 23°C, a l'aide d'un viscosimètre a mobile tournant) . Des exemples de tels agents sont hydroxypropy iméthylcellulose , éthylcellulose , hydroxypropylcellulose, carboxyméthylcellulose, polyéthylèneoxyde, polymères synthétiques et naturels tels que gélatine, gommes, algmate, carraghénates, etc. En tant qu'agent liant, on peut utiliser tout matériau liant, de préférence polymère, classiquement utilisé dans l'art. Des exemples de tels agents sont des dérivés cellulosiques, la polyvinylpyrrolidone, le poly (alcool vinylique) , la gélatine, des gommes, du polyéthylèneoxyde, etc.As a gel-forming agent, any material, preferably polymer, known in the art and which leads to a gel in the presence of water, can be used. The viscosity of this agent is at least 3 mPa.s. (the viscosity is measured for a solution at 1% by weight, at 23 ° C., using a viscometer with a rotating mobile). Examples of such agents are hydroxypropy imethylcellulose, ethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polyethyleneoxide, synthetic and natural polymers such as gelatin, gums, algmate, carrageenans, etc. As binder, any binder material, preferably polymer, conventionally used in the art can be used. Examples of such agents are cellulose derivatives, polyvinylpyrrolidone, polyvinyl alcohol, gelatin, gums, polyethylene oxide, etc.
En tant qu'agent lubrifiant, on peut utiliser tout agent lubrifiant classiquement utilisé dans l'art, per exemple le stéarate de magnésium. Selon un autre mode de réalisation de la composition selon l'invention, dans ledit excipient, l'agent formant un gel est aussi un liant.As lubricating agent, one can use any lubricating agent conventionally used in the art, for example magnesium stearate. According to another embodiment of the composition according to the invention, in said excipient, the gel-forming agent is also a binder.
En tant qu'agent qui à la fois est un agent formant un gel et un agent liant, on peut utiliser tout matériau, de préférence polymère . Des exemples de tels agents sont hydroxypropylméthylcellulose , éthylcellulose , poly¬ éthylèneoxydeAs the agent which is both a gel-forming agent and a binding agent, any material, preferably polymer, can be used. Examples of such agents are hydroxypropylmethylcellulose, ethylcellulose, poly¬ ethyleneoxide
Selon un autre mode de réalisation, dans ledit excipient, l'agent formant un gel et liant présente une viscosité d'au moins 3 mPa.s.According to another embodiment, in said excipient, the gel-forming agent and binder has a viscosity of at least 3 mPa.s.
Par ailleurs, jusqu'à présent il n'a pas été possible de formuler un produit, présentant un dimension raisonnable qui renferme une concentration "élevée en cimetidine, et qui soit efficace à la fois dès son absorption et pendant un temps relativement long, de quelques heures, environ 8 heures .Furthermore, until now it has not been possible to formulate a product, having a reasonable size which contains a "high concentration of cimetidine, and which is effective both from its absorption and for a relatively long time, a few hours, about 8 hours.
La présente invention remédie à cette carence de l'art antérieur, et fournit une association comprenant ;-The present invention remedies this deficiency in the prior art, and provides an association comprising; -
(a) une composition de cimétidi-ne à libération immédiate; et(a) an immediate-release cimetide composition; and
(b) une composition de cimetidine, à libération prolongée selon l'invention.(b) a prolonged-release cimetidine composition according to the invention.
Selon un mode de réalisation, dans l'association selon l'invention, la composition à libération immédiate comprend, en poids :According to one embodiment, in the combination according to the invention, the immediate-release composition comprises, by weight:
(a) 50-99% de cimetidine; et(a) 50-99% cimetidine; and
(b) 1-50% d'un excipient, ledit excipient contenant au moins un liant, un agent lubrifiant et éventuellement un agent de désintégration. Selon un autre mode, ladite composition à libération immédiate comprend, en poids:(b) 1-50% of an excipient, said excipient containing at least one binder, a lubricating agent and optionally a disintegrating agent. According to another mode, said immediate-release composition comprises, by weight:
(a) 75-98% de cimétidme; et(a) 75-98% cimetidme; and
(b) 2-25% dudit excipient. En tant qu'agent de désintégration, on peut utiliser tout matériau classiquement utilisé dans l'art. Des exemples de tels agents sont amidons, carboxyméthylamidons , carboxyméthylcellulose réticulée, polyvinylpyrrolidone réticulée, mélange effervescent (acide plus carbonate) . Selon un mode réalisation, dans l'association selon 1 ' invention: ladite composition de cimétidme à libération immédiate contient de 50 à 400 mg, de préférence de 100 à300 mg et avantageusement environ 200 mg de cimétidme; et ladite composition de cimétidme à libération prolongée contient de 200 à 600 mg, de préférence de 300 à 500 mg et avantageusement environ 400 mg de cimétidme.(b) 2-25% of said excipient. As a disintegrating agent, any material conventionally used in the art can be used. Examples of such agents are starches, carboxymethyl starches, crosslinked carboxymethylcellulose, crosslinked polyvinylpyrrolidone, effervescent mixture (acid plus carbonate). According to one embodiment, in the combination according to the invention: said immediate release cimetidme composition contains from 50 to 400 mg, preferably from 100 to 300 mg and advantageously about 200 mg of cimetidme; and said sustained release cimetidme composition contains from 200 to 600 mg, preferably from 300 to 500 mg and preferably about 400 mg of cimetidme.
Selon une variante avantageuse, l'association selon l'invention est sous la forme d'une gélule contenant lesdites compositions de cimetidine sous la forme de comprimés.According to an advantageous variant, the combination according to the invention is in the form of a capsule containing the said cimetidine compositions in the form of tablets.
Cette forme de dosage unitaire est tout à fait adaptée à une administration par voie orale, et offre, dès son ingestion, un effet thérapeutique, qui se prolonge dans le temps sur quelques heures.This unit dosage form is entirely suitable for oral administration, and offers, from its ingestion, a therapeutic effect, which is extended over time over a few hours.
En tant que gélule, on peut utiliser toute gélule appropriée classiquement utilisée dans l'art. Des exemples de telles gélules sont les gélules, par exemple en gélatine dure, mises dans le commerce par Capsugel, Eli-lilly, Scherer.As a capsule, any suitable capsule conventionally used in the art can be used. Examples of such capsules are the capsules, for example hard gelatin, commercially available from Capsugel, Eli-lilly, Scherer.
Pour la préparation des formes de dosage, des composi ions, et autres, on utilise les procèdes classiquement utilisés dans l'art, tels que la granulation, la compression, et le remplissage de gélules, etc. L'invention a encore pour objet la composition selon l'invention, pour son utilisation en tant que médicament pour le traitement de l'acidité gastrique. L'invention a encore pour objet l'association selon l'invention, pour son utilisation en tant que médicament pour le traitement de l'acidité gastrique.For the preparation of dosage forms, compositions, and the like, the methods conventionally used in the art are used, such as granulation, compression, and filling of capsules, etc. A subject of the invention is also the composition according to the invention, for its use as a medicament for the treatment of gastric acidity. Another subject of the invention is the association according to the invention, for its use as a medicament for the treatment of gastric acidity.
Un autre avantage de l'invention est que le principe actif, la cimetidine, est présent en une quantité majoritaire par rapport à l'excipient, ce qui permet la réalisation de formes de dosage de volume très réduit. Ainsi, les formes de dosage que fournit l'invention, et notamment l'association selon l'invention, de volume réduit, mais contenant une quantité élevée de principe actif, sont particulièrement appropriée pour une administration par voie orale et sont parfaitement acceptées par les patients.Another advantage of the invention is that the active principle, cimetidine, is present in a majority amount relative to the excipient, which allows the realization of dosage forms of very reduced volume. Thus, the dosage forms which the invention provides, and in particular the combination according to the invention, of reduced volume, but containing a high amount of active principle, are particularly suitable for administration by the oral route and are perfectly accepted by patients.
L'invention est maintenant décrite plus en détail en référence aux figures, dans lesquelles: La figure 1 est une coupe de la gélule selon l'invention;The invention is now described in more detail with reference to the figures, in which: FIG. 1 is a section of the capsule according to the invention;
La figure 2 représente la dissolution in vitro d'une association médicamenteuse selon l'invention en fonction du temps;FIG. 2 represents the in vitro dissolution of a drug combination according to the invention as a function of time;
Les figures 3a et 3b représentent, respectivement, le pH moyen de l'estomac et la concentration plasmatique moyenne de cimetidine en fonction du temps.Figures 3a and 3b show, respectively, the average pH of the stomach and the average plasma concentration of cimetidine as a function of time.
En référence à la figure 1, la gélule (1) contient un comprimé (2) correspondant à une composition à libération rapide et le comprimé (3) correspondant à une composition à libération prolongée.Referring to Figure 1, the capsule (1) contains a tablet (2) corresponding to a rapid-release composition and the tablet (3) corresponding to a prolonged-release composition.
Les exemples suivants illustrent l'invention sans toutefois en limiter la portée. Exemple 1 :The following examples illustrate the invention without, however, limiting its scope. Example 1:
On prépare de façon classique deux comprimés, qui sont destinés à être placés dans une gélule, par exemple une gélule de gélatine dure :Two tablets are conventionally prepared, which are intended to be placed in a capsule, for example a hard gelatin capsule:
- Composition en mg du comprimé à libération immédiate: Cimetidine 200- Composition in mg of the immediate-release tablet: Cimetidine 200
Methocel E15LV (hydroxypropyl méthylcellulose) 6 Carboxyméthylcellulose de sodium 10Methocel E15LV (hydroxypropyl methylcellulose) 6 Sodium carboxymethylcellulose 10
Stéarate de magnésium 2 - Composition en mg du comprimé à libération prolongée: Cimetidine 400 Methocel K15 (hydroxypropyl méthylcellulose) 24 Stéarate de magnésium 4 Exemple 2 -.Magnesium stearate 2 - Composition in mg of the prolonged-release tablet: Cimetidine 400 Methocel K15 (hydroxypropyl methylcellulose) 24 Magnesium stearate 4 Example 2 -.
Selon un procédé classique, on prépare deux comprimés.According to a conventional process, two tablets are prepared.
- Composition en mg du comprimé à libération immédiate: Cimetidine 200 Pharmacoat 606 (hydroxypropyl méthylcellulose) 6 Carboxyméthylcellulose de sodium 10- Composition in mg of the immediate-release tablet: Cimetidine 200 Pharmacoat 606 (hydroxypropyl methylcellulose) 6 Sodium carboxymethylcellulose 10
Stéarate de magnésium 2Magnesium stearate 2
- Composition en mg du comprimé à libération prolongée: Cimetidine 400 Polyox 301 (polyéthylène oxyde) 30 Stéarate de magnésium 4- Composition in mg of the prolonged-release tablet: Cimetidine 400 Polyox 301 (polyethylene oxide) 30 Magnesium stearate 4
Exemple 3 :Example 3:
Cet exemple fournit les données de la dissolution in vitro de la formulation de l'exemple 1. La figure 2 donne le graphe du pourcentage de principe actif libéré en fonction du temps.This example provides the data for the in vitro dissolution of the formulation of Example 1. FIG. 2 gives the graph of the percentage of active principle released as a function of time.
Exemple 4 :Example 4:
Cet exemple donne les résultats d'une étude pharmacocinétique mise en oeuvre sur la base de la formulation selon l'exemple 1. L'étude est effectuée sur des volontaires sains (n=8) . Les résultats, reportés aux figures 3a et 3b, montrent que le pH de l'estomac augmente pendant environ 4 heures, et qu'une bonne corrélation existe entre le pH de l'estomac et la concentration plasmatique en cimetidine. This example gives the results of a pharmacokinetic study carried out on the basis of the formulation according to Example 1. The study is carried out on healthy volunteers (n = 8). The results, reported in Figures 3a and 3b, show that the pH of the stomach increases for about 4 hours, and that a good correlation exists between the pH of the stomach and the plasma concentration of cimetidine.

Claims

REVENDICATIONS
1. Composition comprenant, en poids : (a) 50-99% de cimétidme; et1. Composition comprising, by weight: (a) 50-99% of cimetidme; and
(b) 1-50% d'un excipient, ledit excipient contenant au moins un agent formant un gel, un agent liant et un agent lubrifiant.(b) 1-50% of an excipient, said excipient containing at least one gel-forming agent, a binding agent and a lubricating agent.
2. Composition selon la revendication 1, comprenant, en poids :2. Composition according to claim 1, comprising, by weight:
(a) 75-98% de cimetidine; et(a) 75-98% cimetidine; and
(b) 2-25% dudit excipient.(b) 2-25% of said excipient.
3. Composition selon la revendication 1 ou 2 , comprenant, en poids :3. Composition according to claim 1 or 2, comprising, by weight:
(a) 85-95% de cimetidine; et(a) 85-95% cimetidine; and
(b) 5-15% dudit excipient.(b) 5-15% of said excipient.
4. Composition selon l'une quelconque des revendications 1 à 3, dans laquelle, dans ledit excipient l'agent formant un gel est aussi un liant.4. Composition according to any one of claims 1 to 3, in which, in said excipient, the gel-forming agent is also a binder.
5. Composition selon la revendication 4, dans laquelle l'agent formant un gel et liant présente une viscosité d'au moins 3 mPa .s .5. Composition according to claim 4, in which the gel-forming agent and binder has a viscosity of at least 3 mPa .s.
6. Association comprenant :6. Association including:
(a) une composition de cimetidine à libération immédiate; et(a) an immediate release cimetidine composition; and
(b) une composition de cimetidine, à libération prolongée, selon l'une quelconque des revendications 1 à 5(b) a sustained release cimetidine composition according to any one of claims 1 to 5
7. Association selon la revendication 5, dans laquelle la composition à libération immédiate comprend, en poids:7. Association according to claim 5, in which the immediate-release composition comprises, by weight:
(a) 50-99% de cimétidme; et(a) 50-99% cimetidme; and
(b) 1-50% d'un excipient, ledit excipient contenant au moins un liant, un agent lubrifiant et éventuellement un agent de désintégration. (b) 1-50% of an excipient, said excipient containing at least one binder, a lubricating agent and optionally a disintegrating agent.
8. Association selon la revendication 6 ou 7 , dans laquelle la composition à libération immédiate comprend, en poids:8. Association according to claim 6 or 7, in which the immediate-release composition comprises, by weight:
(a) 75-98% de cimetidine; et (b) 2-25% dudit excipient.(a) 75-98% cimetidine; and (b) 2-25% of said excipient.
9. Association selon l'une quelconque des revendications 6 à 8, dans laquelle: ladite composition de cimétidme à libération immédiate contient de 50 à 400 mg, de préférence de 100 à 300 mg et avantageusement environ 200 mg de cimetidine; et ladite composition de cimétidme à libération prolongée contient de 200 à 600 mg, de préférence de 300 à 500 mg et avantageusement environ 400 mg de cimétidme.9. Association according to any one of claims 6 to 8, in which: said immediate release cimetidme composition contains from 50 to 400 mg, preferably from 100 to 300 mg and advantageously about 200 mg of cimetidine; and said sustained release cimetidme composition contains from 200 to 600 mg, preferably from 300 to 500 mg and preferably about 400 mg of cimetidme.
10. Association selon l'une quelconque des revendications 6 a 9, sous la forme d'une gélule contenant lesdites compositions de cimetidine sous la forme de comprimés.10. Association according to any one of claims 6 to 9, in the form of a capsule containing said cimetidine compositions in the form of tablets.
11. Composition selon l'une quelconque des revendications 1 à 5, pour son utilisation en tant que médicament pour le traitement de l'acidité gastrique.11. Composition according to any one of claims 1 to 5, for its use as a medicament for the treatment of gastric acidity.
12. Association selon l'une quelconque des revendications 6 à 10, pour son utilisation en tant que médicament pour le traitement de l'acidité gastrique. 12. Association according to any one of claims 6 to 10, for its use as a medicament for the treatment of gastric acidity.
PCT/FR1995/001080 1994-08-11 1995-08-11 Novel cimetidine-containing compositions and combinations derived therefrom WO1996004892A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU31800/95A AU3180095A (en) 1994-08-11 1995-08-11 Novel cimetidine-containing compositions and combinations derived therefrom

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR94/09964 1994-08-11
FR9409964A FR2723586A1 (en) 1994-08-11 1994-08-11 NEW COMPOSITIONS CONTAINING CIMETIDINE AND DERIVATIVE ASSOCIATIONS THEREOF

Publications (1)

Publication Number Publication Date
WO1996004892A1 true WO1996004892A1 (en) 1996-02-22

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AU (1) AU3180095A (en)
FR (1) FR2723586A1 (en)
WO (1) WO1996004892A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8329214B2 (en) 1997-01-17 2012-12-11 Laboratoires Fournier S.A. Process for producing fenofibrate tablets

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE658905A (en) * 1964-01-27 1965-07-27 Richardson Merrell Inc
CA1229552A (en) * 1984-07-09 1987-11-24 Audley A. Legore Cimetidine compositions
EP0413061A1 (en) * 1987-04-06 1991-02-20 Alza Corporation Controlled-release oral dosage forms comprising different cellulose ethers
EP0431877A1 (en) * 1989-12-05 1991-06-12 Smithkline Beecham Laboratoires Pharmaceutiques Cimetidine pharmaceutical compositions
EP0439858A1 (en) * 1990-01-31 1991-08-07 Aesculaap B.V. Veterinary phenytoin composition

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE658905A (en) * 1964-01-27 1965-07-27 Richardson Merrell Inc
CA1229552A (en) * 1984-07-09 1987-11-24 Audley A. Legore Cimetidine compositions
EP0413061A1 (en) * 1987-04-06 1991-02-20 Alza Corporation Controlled-release oral dosage forms comprising different cellulose ethers
EP0431877A1 (en) * 1989-12-05 1991-06-12 Smithkline Beecham Laboratoires Pharmaceutiques Cimetidine pharmaceutical compositions
EP0439858A1 (en) * 1990-01-31 1991-08-07 Aesculaap B.V. Veterinary phenytoin composition

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8329214B2 (en) 1997-01-17 2012-12-11 Laboratoires Fournier S.A. Process for producing fenofibrate tablets
US8343540B2 (en) 1997-01-17 2013-01-01 Laboratories Fournier S.A. Process for producing fenofibrate tablets

Also Published As

Publication number Publication date
AU3180095A (en) 1996-03-07
FR2723586A1 (en) 1996-02-16

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