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WO1992009286A1 - Composition renfermant des inhibiteurs des recepteurs h2 a l'histamine ainsi qu'un materiau a adhesion biologique - Google Patents

Composition renfermant des inhibiteurs des recepteurs h2 a l'histamine ainsi qu'un materiau a adhesion biologique Download PDF

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Publication number
WO1992009286A1
WO1992009286A1 PCT/GB1991/002063 GB9102063W WO9209286A1 WO 1992009286 A1 WO1992009286 A1 WO 1992009286A1 GB 9102063 W GB9102063 W GB 9102063W WO 9209286 A1 WO9209286 A1 WO 9209286A1
Authority
WO
WIPO (PCT)
Prior art keywords
histamine
receptor antagonist
treatment
cimetidine
gastric
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/GB1991/002063
Other languages
English (en)
Inventor
Adrian Francis Davis
Mark Coke
John Edward O'mullane
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.)
Beecham Group PLC
Original Assignee
Beecham Group PLC
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 Beecham Group PLC filed Critical Beecham Group PLC
Priority to AU89098/91A priority Critical patent/AU659422B2/en
Priority to JP4500445A priority patent/JPH06502855A/ja
Priority to PL91299319A priority patent/PL168421B1/pl
Publication of WO1992009286A1 publication Critical patent/WO1992009286A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • composition containing antihistamine H2 receptor antagonists and bioadhesive material.
  • This invention relates to the treatment of gastric disorders and pharmaceutical compositions for use therein. More
  • compositions for use in the invention are specifically adapted to provide local delivery across the stomach wall to the H 2 -receptor on the parietal cell receptor.
  • Histamine H 2 -receptor antagonists for example cimetidine, ranitidine, nizetidine and famotidine, reduce acid secretion by acting directly on the acid-secreting parietal cell
  • histamine H 2 -receptor antagonists are remarkably effective in the treatment of many gastric disorders, in particular peptic and gastric ulcers, there exist certain patient groups which do not respond to treatment.
  • non-responders patients, referred to as non-responders, do not respond to conventional histamine H 2 -receptor antagonist therapy.
  • H 2 -receptor antagonist treatment by hypersecreting patients for example critically ill, multiple trauma patients (Martin L. et al. : Failure of cimetidine prophylaxis in the
  • Histamine H 2 -receptor antagonists are of potential benefit in the self-medication of acute, self-limiting gastric disorders such as hyperacidity. However, their slow onset of action is unlikely to meet the consumer requirement for rapid relief of symptoms.
  • sucralfate and other antacids has been investigated.
  • the rationale for co-administration with antacid is that the antacid brings about rapid relief from the symptoms of excess stomach acidity by neutralisation whereas the
  • histamine H 2 -receptor antagonist acts independently by inhibiting secretion of acid from the parietal cell.
  • Histamine H 2 -receptor antagonist - antacid combinations are therefore generally contraindicated.
  • Bioadhesive materials have received considerable attention as platforms for controlled drug delivery. They can be targetted to specific drug administration sites, prolong the residence time and ensure an optimal contact with the absorbing surface. Many different types of bioadhesive materials, both natural and synthetic, can be used in the design of controlled drug delivery systems.
  • sucralfate is a basic aluminium sulphate sucrose complex having ulcer healing and buffering properties. According to the literature, sucralfate has been shown to act by forming a bioadhesive gel structure which is believed to provide a local protective barrier. It has been reported that
  • sucralfate does not interfere with the absorption of
  • histamine H 2 -receptor antagonists histamine H 2 -receptor antagonists. Clinical studies have indicated a combination therapy to be of potential benefit.
  • EP-A-O 286 781 (Heumann Pharma) relates to pharmaceutical preparations with cytoprotective effect on the
  • compositions comprising sucralfate and a therapeutically effective amount of a medicament which is a) substantially water insoluble, or b) a mixture of a water-soluble medicament and a release-delaying material which on admixture forms a substantially water-insoluble medicament.
  • the medicament is selected from the group consisting of inter alia antacids and anti-ulcer medicaments.
  • sucralfate plus antacid and sucralfate plus an anti-ulcer medicament are described as cytoprotective compositions, useful in the treatment of peptic ulcers by forming an ulcer-adherent protective gel barrier.
  • EP-A-O 193 400 (Reckitt and Colman) describes pharmaceutical compositions comprising mixtures of a histamine H 2 -receptor antagonist and sodium polyacrylate in the weight ratio 10 : 1 to 1 : 10.
  • the compositions are described for use in the treatment of gastritis or of gastro-duodenal ulcers.
  • the compositions may include an antacid.
  • Use of antacid is described as resulting in a reduction in the viscosity of the liquid compositions, thereby providing some degree of viscosity control in the design of readily pourable liquid preparations.
  • US 4,615,697 discloses a controlled release composition
  • a treating agent which may be a medicament
  • a bioadhesive material which is a water-swellable and water-insoluble, fibrous, cross-linked carboxy-functional polymer.
  • the controlled release compositions are described as adhering to the skin or to mucous membranes in the presence of water.
  • Cimetidine is listed as an example of a medicament.
  • Current treatments using histamine H 2 -receptor antagonists act systemically, i.e. the histamine H 2 -receptor antagonist is delivered to the parietal cell receptor from the blood.
  • bioavailability of the histamine H 2 -receptor antagonist increases the capacity of the histamine H 2 -receptor
  • sucralfate buffered at or around the pKa of the histamine H 2 -receptor antagonist, provides an effective therapy for gastric disorders, mediated through local delivery of the histamine H 2 -receptor antagonist directly into the parietal cell receptor of the stomach wall.
  • the present invention provides the use of an orally administrable pharmaceutical composition comprising a histamine H 2 -receptor antagonist and a bioadhesive material, for the manufacture of a medicament for the treatment of gastric disorders, characterised in that the composition is formulated as an intimate mixture whereby the bioadhesive material and the histamine H 2 -receptor antagonist form, in situ, a bioadhesive complex, locally targeting the histamine H 2 -receptor antagonist to the stomach wall; and the
  • composition is optimally buffered to confer a pH
  • the invention also provides a method of treatment of gastric disorders comprising administering to a sufferer an
  • composition comprising an intimate mixture of a histamine H 2 -receptor antagonist and a bioadhesive material forming in situ a bioadhesive complex; and a buffering component to confer a pH substantially equal to that of the pKa of the histamine H 2 -receptor antagonist.
  • the invention provides a locally acting pharmaceutical composition for use in the treatment of gastric disorders which comprises an intimate mixture of a histamine H 2 -receptor antagonist and a bioadhesive material, and a buffering component to confer a pH substantially equal to that of the pKa of the histamine H 2 -receptor antagonist.
  • Bioadhesive materials for use in compositions of the present invention include materials, both natural and synthetic, which are capable of adhering to biological surfaces such as mucus membranes.
  • bioadhesive materials include natural gums and plant extracts and synthetic materials such as sucralfate, cellulose derivatives, acrylic acid and methacrylic acid derivatives, for example cross-linked acrylic and methacrylic acid copolymers available under the Trade Names CARBOPOL and POLYCARBOPHIL .
  • compositions for use in the invention are optimally buffered by the use of a buffering component which is suitably an antacid having equilibrium pH, acid neutralising capacity and gastric residence time values which provide a pH profile with time conferring a local pH level substantially equal to that of the pKa of the histamine H 2 -receptor antagonist.
  • a buffering component which is suitably an antacid having equilibrium pH, acid neutralising capacity and gastric residence time values which provide a pH profile with time conferring a local pH level substantially equal to that of the pKa of the histamine H 2 -receptor antagonist.
  • H 2 -RA therapy fails in Zollinger-Ellison syndrome due to low levels of the drug at the H 2 -receptor of the parietal cells.
  • Local delivery according to the invention which increases the concentration of drug at the H 2 -receptors of the parietal cell and renders the histamine H 2 -receptor antagonist effective at low dosage levels, is regarded as of particular benefit in the
  • Histamine H 2 -receptor antagonists for use in compositions of the invention include cimetidine, ranitidine and famotidine, preferably cimetidine and ranitidine, and especially
  • pKa values for known histamine H 2 -receptor antagonists are readily available from pharmacological publications.
  • compositions of the invention include aluminium hydroxide, magnesium hydroxide, aluminium hydroxide-magnesium carbonate co-dried gel, magnesium carbonate, magnesium oxide,
  • phosphoric acid and combinations thereof.
  • Further suitable antacids may be selected by pharmacokinetic analysis of the acid-secretion reducing capacity of a selected histamine H 2 -receptor antagonist using a
  • the model may be used to describe pharmacokinetics for a selected histamine
  • Gastric pH levels are influenced by antacid.
  • antacid By inserting known values for equilibrium pH, acid neutralising capacity and gastric residence time, the suitability of any given antacid may be determined.
  • histamine H 2 -receptor antagonist therapies act systemically and drug is distributed to all parts of the body via the bloodstream. Hence, it will be appreciated that non-target body tissues are exposed to drug.
  • An advantage of a locally targeted drug delivery system is that low doses may be used and thus pharmacologically relevant doses are not achieved in non-target tissues.
  • Excretion of histamine H 2 -receptor antagonist into the stomach lumen from the parietal cell tissue receptor causes a reduction in local bioavailability of the antagonist whilst gastric absorption of histamine H 2 -receptor
  • An advantageous feature of the invention is the potential for using reduced dose levels of histamine H 2 -receptor
  • the dose level of histamine H 2 -receptor antagonist may be selected according to the potency of the antagonist on a weight basis and according to the severity of the condition.
  • the histamine H 2 -receptor antagonist is cimetidine or ranitidine it may be present in an amount from about 1 mg to 800 mg per dosage form, typically from about 5 mg to 50 mg for example 5, 10, 15, 20 or 25 mg.
  • treatment with the present compositions provides a more rapid onset of action which renders them particularly suitable for the treatment of acute gastritis.
  • a further aspect of the invention is that the amount of antacid present in any given composition is independent of the dose of histamine H 2 -receptor antagonist.
  • the bioadhesive material for example sucralfate, may be present in an amount from about 100 mg to 1500 mg per dosage form, typically from about 800 mg to 1200 mg, for example 1000 mg. These dosage levels encompass compositions where sucralfate serves as the buffering component and which do not include a further buffering agent. Where a composition includes a bioadhesive material which has no buffering capacity or, in addition to sucralfate includes a further buffering agent, the level of buffer is optimally chosen to confer a pH substantially equal to that of the pKa of the histamine H 2 -receptor antagonist.
  • the buffering component serves a dual role. In one aspect, in the accepted mode of action of antacids, it brings about relief from the symptoms of excess stomach acidity by neutralisation. In a second aspect, and more importantly, it serves to act as an appropriate
  • buffered vehicle to enhance the absorption of the histamine H 2 -receptor antagonist.
  • the dose of buffering agent may be selected to achieve both effects.
  • a suitable dose range for magnesium hydroxide is from about 150 mg to 3000 mg, for example from about 300 mg to 1500 mg, such as from about 300 mg to 600 mg.
  • a suitable dose range for aluminium hydroxide is from about 180 mg to 3600 mg, for example from about 360 mg to 1800 mg, such as from 360 to 720 mg.
  • a suitable dose range for sodium bicarbonate is from about 400mg to 8,000mg for example from about 800 mg to 4000mg, such as from about 800mg to 1600mg.
  • compositions for use in the present invention may also contain pharmaceutically acceptable carriers.
  • Compositions may be formulated for oral administration in solid or liquid form, for example as tablets, capsules, powders, suspensions or dispersions. Compositions may thus be formulated by admixture with pharmaceutically acceptable vehicles
  • compositions additionally containing, as desired, pharmaceutically acceptable adjuvants including inter alia thickeners, preservatives, and colouring and flavouring agents.
  • compositions for use in the present invention are novel and as such form a further aspect of the invention.
  • sucralfate as the bioadhesive material but are not limited thereto. Any material having
  • bioadhesive properties either a natural or synthetic material, may be incorporated into compositions for use in the invention.
  • Cimetidine Entrapment of Cimetidine in Sucralfate Cimetidine solutions were made up at pH 2.5 at
  • the level of entrapment of cimetidine in sucralfate and the release of the entrapped cimetidine into ceon as a function of time was determined.
  • the levels of cimetidine studied were 0, 25, 50, 75, 100 and 125 mg/ml in a 50 ml volume.
  • hydrochloric acid (30ml). The solution was mixed using a magnetic stirrer. A pH probe was inserted into the solution and 1M
  • hydrochloric acid was added until a clear solution (pH 2.5) was obtained. The volume was made up to 50ml. A 200 ⁇ l sample was removed. Sucralfate (2g ex Katsura) was added with stirring and allowed to disperse. 1 M HCl was added in 200 ⁇ l aliquots until paste formation occurred. Stirring was continued until the supernatant was clear. A 200 ⁇ l sample of
  • 0.1M HCl 50ml was added, the mixture swirled for 10 seconds and a 200 ⁇ l sample removed. A further 50ml sample of 0.1 M HCl was added. A 200 ⁇ l sample was removed. A third 50ml sample of 0.1M HCl (pH 1.5) was added. The resulting mixture was placed on an orbital shaker (GFL.3017) at 3/4 maximum speed.
  • sucralfate was added to dissolve the sucralfate. This final solution was diluted and the total final level of sucralfate was determined
  • Each of the 200 ⁇ l samples removed throughout the experment was assayed as follows: a 50 ⁇ sample was transferred to a vial and 1.95 ml. 0.1 M HCl was added. Further dilutions with distilled water were made as necessary. Optical density at 218mm was determined versus a distilled water blank.
  • the release data indicates that release from sucralfate is a diffusional process.
  • the rate of cimetidine release from sucralfate as a function of pH was determined at pH values 1.5, 3.0, 4.5, 6.0 and 7.5.
  • the experiment was carried out using a cimetidine concentration of 50 mg/ml and 1g sucralfate.
  • Powder Formulations The ingredients are dry blended under conditions of
  • the active antacid ingredients are granulated or spray dried in a conventional manner.
  • H 2 -receptor antagonist and the bioadhesive material are blended along with conventional tabletting aids, fillers and palatability aids and the blend is tabletted on a
  • Aluminium hydroxide and magnesium hydroxide are received as commercially available suspensions. These active
  • flavours as appropriate.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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Abstract

Compositions pharmaceutiques tamponnées destinées au traitement local des troubles gastriques et comportant un inhibiteur des récepteurs H2 à l'histamine mélangé de manière intime à un matériau à adhésion biologique.
PCT/GB1991/002063 1990-11-27 1991-11-21 Composition renfermant des inhibiteurs des recepteurs h2 a l'histamine ainsi qu'un materiau a adhesion biologique Ceased WO1992009286A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU89098/91A AU659422B2 (en) 1990-11-27 1991-11-21 Composition containing antihistamine H2 receptor antagonists and bioadhesive material
JP4500445A JPH06502855A (ja) 1990-11-27 1991-11-21 抗ヒスタミンｈ↓２受容体拮抗剤および生体接着剤を含有する組成物
PL91299319A PL168421B1 (en) 1990-11-27 1991-11-21 Method of obtaining a pharmaceutic composition for treating stomach disorders

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9025710.6 1990-11-27
GB909025710A GB9025710D0 (en) 1990-11-27 1990-11-27 Novel treatment

Publications (1)

Publication Number Publication Date
WO1992009286A1 true WO1992009286A1 (fr) 1992-06-11

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ID=10686017

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PCT/GB1991/002063 Ceased WO1992009286A1 (fr) 1990-11-27 1991-11-21 Composition renfermant des inhibiteurs des recepteurs h2 a l'histamine ainsi qu'un materiau a adhesion biologique

Country Status (9)

Country Link
EP (1) EP0559812A1 (fr)
JP (1) JPH06502855A (fr)
AU (1) AU659422B2 (fr)
CA (1) CA2096962A1 (fr)
GB (1) GB9025710D0 (fr)
IE (1) IE914091A1 (fr)
PL (1) PL168421B1 (fr)
WO (1) WO1992009286A1 (fr)
ZA (1) ZA919290B (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4139883A1 (de) * 1991-11-29 1993-06-03 Michael Prof Dr Dittgen Verfahren zur herstellung bioadhaesiver arzneimittel
WO1995001784A1 (fr) * 1993-07-06 1995-01-19 Merck & Co., Inc. Composes anti-flatulences a base d'antagoniste d'h2 et de sucralfate
WO1995010274A1 (fr) * 1993-10-14 1995-04-20 F.H. Faulding & Co. Limited Composition pharmaceutique aqueuse
WO1995027486A1 (fr) * 1994-04-12 1995-10-19 Glaxo Group Limited Compositions faiblement dosees en ranitidine destinees au traitement de troubles gastro-intestinaux mineurs lies a un exces de secretion acide
US5593696A (en) * 1994-11-21 1997-01-14 Mcneil-Ppc, Inc. Stabilized composition of famotidine and sucralfate for treatment of gastrointestinal disorders
US6319513B1 (en) 1998-08-24 2001-11-20 The Procter & Gamble Company Oral liquid mucoadhesive compounds
WO2023218480A1 (fr) * 2022-05-09 2023-11-16 Syri Research Private Limited Formulation orale liquide de famotidine ou d'un sel pharmaceutiquement acceptable de celle-ci

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TR199701092T1 (xx) * 1995-04-03 1998-01-21 Chugai Seiyaku Kabushiki Kaisha Et Al Sukralfat içeren farmakotik kompozisyonlar.
WO1997028823A1 (fr) * 1996-02-08 1997-08-14 Chugai Seiyaku Kabushiki Kaisha Procede d'utilisation d'un agent antiacide et preparation pharmaceutique le contenant
KR20010033001A (ko) * 1998-04-01 2001-04-25 나가야마 오사무 알콜성 위염 예방제

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0286781A2 (fr) * 1987-03-30 1988-10-19 HEUMANN PHARMA GMBH & CO Préparation pharmaceutique pour le traitement des maladies des voies gastro-intestinales
EP0381414A2 (fr) * 1989-01-30 1990-08-08 E.R. Squibb & Sons, Inc. Composition anti-ulcéreuse
EP0403048A2 (fr) * 1989-06-14 1990-12-19 Warner-Lambert Company Un modèle de structure de système craniomandibulaire humain

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0286781A2 (fr) * 1987-03-30 1988-10-19 HEUMANN PHARMA GMBH & CO Préparation pharmaceutique pour le traitement des maladies des voies gastro-intestinales
EP0381414A2 (fr) * 1989-01-30 1990-08-08 E.R. Squibb & Sons, Inc. Composition anti-ulcéreuse
EP0403048A2 (fr) * 1989-06-14 1990-12-19 Warner-Lambert Company Un modèle de structure de système craniomandibulaire humain

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Chemical Abstracts, volume 103, no. 17, 1985 (Columbus, Ohio, US) S. Bank et al. "Prevention of duodenal ulcers in the rat using a combination of ranitidine and sucralfate in subtherapeutic doses", see page 66, abstract 134872q, & Gut, 1985, 26(6), 603-6 *
Chemical Abstracts, volume 106, no. 9, 1987, (Columbus, Ohio, US) G. Mullersman et al.: "Lack of clinically significant in vitro and in vivo interactions between ranitidine and sucralfate", see page 19, abstract 60798h, & J. Pharm. Sci., 1986, 75(10), 995-8 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4139883A1 (de) * 1991-11-29 1993-06-03 Michael Prof Dr Dittgen Verfahren zur herstellung bioadhaesiver arzneimittel
WO1995001784A1 (fr) * 1993-07-06 1995-01-19 Merck & Co., Inc. Composes anti-flatulences a base d'antagoniste d'h2 et de sucralfate
WO1995010274A1 (fr) * 1993-10-14 1995-04-20 F.H. Faulding & Co. Limited Composition pharmaceutique aqueuse
WO1995027486A1 (fr) * 1994-04-12 1995-10-19 Glaxo Group Limited Compositions faiblement dosees en ranitidine destinees au traitement de troubles gastro-intestinaux mineurs lies a un exces de secretion acide
AU690664B2 (en) * 1994-04-12 1998-04-30 Glaxo Group Limited Low dosage ranitidine compositions for the treatment of minor gastrointestinal disorders associated with excess acid secretion
US5593696A (en) * 1994-11-21 1997-01-14 Mcneil-Ppc, Inc. Stabilized composition of famotidine and sucralfate for treatment of gastrointestinal disorders
US6319513B1 (en) 1998-08-24 2001-11-20 The Procter & Gamble Company Oral liquid mucoadhesive compounds
WO2023218480A1 (fr) * 2022-05-09 2023-11-16 Syri Research Private Limited Formulation orale liquide de famotidine ou d'un sel pharmaceutiquement acceptable de celle-ci

Also Published As

Publication number Publication date
JPH06502855A (ja) 1994-03-31
AU659422B2 (en) 1995-05-18
GB9025710D0 (en) 1991-01-09
ZA919290B (en) 1992-09-30
AU8909891A (en) 1992-06-25
PL168421B1 (en) 1996-02-29
EP0559812A1 (fr) 1993-09-15
IE914091A1 (en) 1992-06-03
CA2096962A1 (fr) 1992-05-28

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