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WO1997017960A1 - Composition pharmaceutique contenant de l'amoxycilline, du clavulanate ainsi qu'un dessiccatif - Google Patents

Composition pharmaceutique contenant de l'amoxycilline, du clavulanate ainsi qu'un dessiccatif Download PDF

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Publication number
WO1997017960A1
WO1997017960A1 PCT/EP1996/005049 EP9605049W WO9717960A1 WO 1997017960 A1 WO1997017960 A1 WO 1997017960A1 EP 9605049 W EP9605049 W EP 9605049W WO 9717960 A1 WO9717960 A1 WO 9717960A1
Authority
WO
WIPO (PCT)
Prior art keywords
desiccating
metal salt
composition
composition according
oral administration
Prior art date
Application number
PCT/EP1996/005049
Other languages
English (en)
Inventor
Teodoro Fonio
Marco Pesatori
Diego Oldani
Original Assignee
Smithkline Beecham S.P.A.
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 Smithkline Beecham S.P.A. filed Critical Smithkline Beecham S.P.A.
Publication of WO1997017960A1 publication Critical patent/WO1997017960A1/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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems

Definitions

  • the present invention relates to pharmaceutical compositions for oral administration in the treatment of bacterial infections.
  • the invention relates to compositions comprising the antibiotic amoxycillin in the form of its trihydrate and the beta-lactamase inhibitor clavulanic acid in the form of potassium clavulanate.
  • Potassium clavulanate is extremely moisture sensitive, and compositions which include it normally need to be desiccated.
  • GB 2005384 discloses pharmaceutical compositions suitable for oral administration which use colloidal silica in the form of Syloid TM as a desiccant
  • EP 0049061 discloses pharmaceutical compositions for oral administration which comprise amoxycillin trihydrate and potassium clavulanate, and further types of desiccant which are edible.
  • PCT/EP 95/02127 discloses compositions suitable for injection or infusion which comprise potassium clavulanate and sodium amoxycillin, and which use inter alia desiccating metal salts as desiccants.
  • the present invention provides a solid pharmaceutical composition suitable for oral administration, which composition comprises amoxycillin trihydrate, potassium clavulanate and a desiccant wherein the desiccant comprises a desiccating metal salt which is pharmaceutically acceptable by oral administration.
  • the solid composition of the invention may for example be a tablet formulation in which one or more such tablets provide a unit dose of the active ingredients amoxycillin trihydrate and potassium clavulanate.
  • the solid composition of the invenuon may alternatively for example be a granulate formulation, either provided in a unit dose quantity such as in a sachet or provided in a bulk of several unit dose quantities for subdivision into unit doses, or for subsequent compaction to form a tablet.
  • the weights of amoxycillin trihydrate and potassium clavulanate are referred to herein in terms of the weights of the corresponding pure parent free acids (pfa) amoxycillin and clavulanic acid respectively.
  • the weight ratio of amoxycillin to clavulanic acid in the pharmaceutical composition of the present invenuon is from 30 .1 to 2:1 for example from 15:1 to 2:1, for example 8: 1, 7: 1, 6: l or 4: l ⁇ 10%.
  • the oral unit dose quantity of a composition of this invention will contain from 125 mg to 1250 mg of amoxycillin, for example it may contain about 125, 250, 500, 875 or 1000 mg of amoxycillin.
  • the oral unit dose quantity of a composition of this invention will contain from 20 to 300 mg of clavulanic acid for example it may contain about 25, 31.25, 50, 62.5, 100, 120, 125, 150, 200, 250 or 300 mg of clavulanic acid.
  • the amounts of amoxycillin trihydrate and potassium clavulanate in the compositions of this invention may be similar to those in known solid compositions intended for oral administration.
  • a suitable desiccating form of magnesium chloride is an at least partly dehydrated form, for example obtainable by heat treatment of magnesium chloride hexahydrate under vacuum until it has a water content less than 40 wt. %.
  • Other metal salts which may be suitable include disodium phosphate in an at least partly anhydrous form e.g. containing around 0.1% water. Such salts may be used singly or in mixtures, for example a mixture of sodium chloride and magnesium chloride.
  • the quantity of a desiccating metal salt needed to provide adequate desiccation of the pharmaceutical composition of the invention will depend upon the quantity of the amoxycillin trihydrate and potassium clavulanate in the composition but can easily be determined by experimentation, for example by determination of the stabilisation of the amoxycillin trihydrate and potassium clavulanate content
  • compositions may contain one or more conventional excipients as appropriate to the solid form, for example fillers such as micro-crystalline cellulose, lubricants such as magnesium stearate, disintegrants such as sodium starch glycollate, crosslinked polyvinyl pyrrolidone or other similar known agents, granulating aids etc.
  • excipients such as micro-crystalline cellulose, lubricants such as magnesium stearate, disintegrants such as sodium starch glycollate, crosslinked polyvinyl pyrrolidone or other similar known agents, granulating aids etc.
  • such compositions may contain flavouring agents, preservatives and colouring agents.
  • the materials present in such compositions should have low free moisture contents and preferably be pre-dried. Tightly bound water, such as water of crystallisation normally has little adverse effect on stability.
  • the desiccating metal salt may be incorporated within the solid form.
  • the desiccating metal salt may suitably be included within the compacted tablet
  • the desiccating metal salt may be included within the granulates, or additionally or alternatively the desiccating metal salt may be included externally to the granulates together with the granulates in a suitable moisture-tight contaner such as a sachet
  • compositions of the present invention are suitably packaged in protective packages such as, for example, screw-cap bottles, aluminium foil sachets and aluminium blister packs.
  • a process for the preparation of a tablet composition as hereinbefore described which comprises bringing into association the components of said composition and thereafter compressing the blended mixture into a tablet.
  • the process by which a tablet solid form is made may be one in which the powdered ingredients are directly compressed in a die, or alternatively the ingredients may be pre-granulated then tabletted.
  • the granulation process is a dry granulation process such as slugging or roller compaction then milling.
  • a process for the preparation of a granulate composition as hereinbefore described which comprises bringing into association the components of said composition and thereafter forming the blended mixture into granules.
  • the granulation process is a dry granulation process such as slugging or roller compaction then milling.
  • the composition of the composition is carried out in a dry atmosphere, e.g. one containing less than 30% relative humidity and preferably one containing less than 20% relative humidity. Such dryness is desirable for the preservation of the highly moisture sensitive potassium clavulanate.
  • the present invention also provides the use of such a composition in the preparation of a medicament for oral administration in the treatment of bacterial infections.
  • composition of these three batches is as follows per tablet:
  • the tablets were made by preparing a standard production final mixture for amoxycillimpotassium clavulanate tablets, without SyloidTM or magnesium chloride. This mixture was divided into three parts: - the first part was directly tabletted, obtaining batch (A). - the second part was mixed with Syloid AL-1TM and then tabletted obtaining batch (B).
  • Such tablets could be milled by known processes to form a granulate composition of this invention.

Landscapes

  • 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)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Cette composition pharmaceutique sous forme solide et destinée à une administration par voie orale comprend un trihydrate d'amoxycilline, du clavulanate de potassium ainsi qu'un dessiccatif, ce dernier comportant un sel de métal dessiccatif acceptable sur le plan pharmacologique en vue d'une administration par voie orale.
PCT/EP1996/005049 1995-11-16 1996-11-15 Composition pharmaceutique contenant de l'amoxycilline, du clavulanate ainsi qu'un dessiccatif WO1997017960A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT95MI002354A ITMI952354A1 (it) 1995-11-16 1995-11-16 Composizione farmaceutica
ITMI95A002354 1995-11-16

Publications (1)

Publication Number Publication Date
WO1997017960A1 true WO1997017960A1 (fr) 1997-05-22

Family

ID=11372531

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1996/005049 WO1997017960A1 (fr) 1995-11-16 1996-11-15 Composition pharmaceutique contenant de l'amoxycilline, du clavulanate ainsi qu'un dessiccatif

Country Status (2)

Country Link
IT (1) ITMI952354A1 (fr)
WO (1) WO1997017960A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1902708A1 (fr) * 2006-09-25 2008-03-26 Losan Pharma GmbH Compositions pharmaceutiques stabilisées et solides contenant au moins un médicament et procédé d'élaboration

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2005538A (en) * 1977-10-11 1979-04-25 Beecham Group Ltd Compositions containing amoxycillin trihydrate and potassium clavulanate
EP0049061A1 (fr) * 1980-09-27 1982-04-07 Beecham Group Plc Formulation pharmaceutique
WO1996001109A1 (fr) * 1994-07-05 1996-01-18 Smithkline Beecham Plc Compositions pharmaceutiques a base de clavulanate

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2005538A (en) * 1977-10-11 1979-04-25 Beecham Group Ltd Compositions containing amoxycillin trihydrate and potassium clavulanate
EP0049061A1 (fr) * 1980-09-27 1982-04-07 Beecham Group Plc Formulation pharmaceutique
WO1996001109A1 (fr) * 1994-07-05 1996-01-18 Smithkline Beecham Plc Compositions pharmaceutiques a base de clavulanate

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"ORGANIKUM ORGANISCH-CHEMISCHES GRUNDPRAKTIKUM", 1974, VEB DEUTSCHER VERLAG DER WISSENSCHAFTEN, BERLIN, XP002024871 *
DR. HERBERT FIEDLER: "LEXIKON DER HILFSSTOFFE FÜR PHARMAZIE, KOSMETIK UND ANGRENZENDE GEBIETE", 1989, EDITIO CANTOR, AULENDORF, XP002024872 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1902708A1 (fr) * 2006-09-25 2008-03-26 Losan Pharma GmbH Compositions pharmaceutiques stabilisées et solides contenant au moins un médicament et procédé d'élaboration
WO2008037359A3 (fr) * 2006-09-25 2008-06-26 Losan Pharma Gmbh Formes galéniques solides stabilisées, et leur procédé de production
US9775807B2 (en) 2006-09-25 2017-10-03 Losan Pharma Gmbh Stabilized solid medicinal forms containing active ingredient and method for the production thereof
US10206879B2 (en) 2006-09-25 2019-02-19 Losan Pharma Gmbh Active ingredient containing stabilised solid forms and method for the production thereof
US10603280B2 (en) 2006-09-25 2020-03-31 Losan Pharma Gmbh Active ingredient containing stabilised solid medicinal forms and methods for the production thereof

Also Published As

Publication number Publication date
ITMI952354A0 (fr) 1995-11-16
ITMI952354A1 (it) 1997-05-16

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