WO2005067895A1 - Compositions pharmaceutiques a liberation controlee - Google Patents

Compositions pharmaceutiques a liberation controlee Download PDF

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Publication number
WO2005067895A1
WO2005067895A1 PCT/EP2005/000322 EP2005000322W WO2005067895A1 WO 2005067895 A1 WO2005067895 A1 WO 2005067895A1 EP 2005000322 W EP2005000322 W EP 2005000322W WO 2005067895 A1 WO2005067895 A1 WO 2005067895A1
Authority
WO
WIPO (PCT)
Prior art keywords
controlled release
water soluble
soluble hydrophilic
formulation according
sodium
Prior art date
Application number
PCT/EP2005/000322
Other languages
English (en)
Inventor
Seetharaman Sritharan
Harsha M. Dabhade
Sunilendu Bhushan Roy
Original Assignee
Sandoz Ag
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 Sandoz Ag filed Critical Sandoz Ag
Publication of WO2005067895A1 publication Critical patent/WO2005067895A1/fr

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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
    • A61K9/20—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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • 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
    • 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
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • 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

  • This invention relates to pharmaceutical compositions of the I-acetoxyethyl ester of the antibiotic compound cefuroxime, known as cefuroxime axetil. More particularly this invention relates to controlled release formulations of cefuroxime axetil and a process for the preparation thereof.
  • Drugs containing an active ingredient with a relatively short biological half life often need to be administered several times a day in order to achieve the desired therapeutic effect.
  • controlled delivery systems have been developed which avoid the need for such multiple administrations. Controlled release systems not only reduce the frequency of administration but also contribute to improved patient compliance and can reduce side effects.
  • one object of the present invention is the provision of a controlled release formulation of cefuroxime axetil.
  • the present invention provides a controlled release pharmaceutical formulation comprising cefuroxime axetil and a water soluble hydrophilic agent.
  • a suitable water soluble hydrophilic agent according to the present invention is sodium chloride.
  • the present invention provides a process for the preparation of a controlled release pharmaceutical formulation of cefuroxime axetil comprising mixing cefuroxime axetil with a water soluble hydrophilic agent.
  • the cefuroxime axetil may be in any form, e.g. in a crystalline form, an amorphous form, or in the form of a solid solution in a polymer.
  • the cefuroxime axetil is in the form of a solid solution in a polymer.
  • Suitable polymers include homo- and copolymers of a polyvinylpyrrolidone, polyethylene glycol, polyethylene oxide and cellulose.
  • Suitable water soluble hydrophilic agents are those having a solubility in water at room temperature of at least 1mg/1000ml.
  • Suitable water soluble hydrophilic agents include sodium chloride, potassium chloride, sulphates of sodium, potassium or magnesium, citric acid and salts thereof, lactic acid and salts thereof, fumaric acid and salts thereof, sodium carbonate, sodium bicarbonate, sodium lauryl sulphate, lactose, sucrose, tween, polyethylene glycol, mannitol, sorbitol and cetrimide.
  • Preferred water soluble hydrophilic agents include sodium chloride, potassium chloride, sulphates of sodium, potassium or magnesium, citric acid and salts thereof, lactic acid and salts thereof, fumaric acid and salts thereof, sodium carbonate and sodium bicarbonate,. More preferred water soluble hydrophilic agents include sodium chloride, potassium chloride, sulphates of sodium, potassium or magnesium. In particular preferred water soluble hydrophilic agents are sodium chloride or potassium chloride.
  • the cefuroxime axetil active ingredient and the water soluble hydrophilic agent are preferably present in a ratio between the range of 1 :0.1 to 0.1:1.
  • the amount of water soluble hydrophilic agent in the formulations of the present invention is preferably at least 5% by weight, e.g. at least 10% by weight.
  • a formulation according to the present invention may optionally comprise a rate controlling polymer or a mixture of rate controlling polymers.
  • Suitable rate controlling polymers include water soluble polymers, for instancecellulose derivatives, acrylic acid derivatives, polyoxyethylene glycols and polyvinyl alcohols. Polysaccharides or N-vinyl-2- pyrrolidone/vinyl acetate copolymers are excluded.
  • Preferred rate controlling polymers are cellulose derivatives and acrylic acid derivatives. Suitable cellulose derivatives include carboxymethyl cellulose, calcium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose and ethyl cellulose.
  • a preferred rate controlling polymer is a commercially available hydroxypropylmethyl cellulose e.g. Methocel K 4 MCR, Methocel K 4 M Premium. If desired, variation of the dissolution profile can be achieved by adjusting the ratio between the water soluble hydrophilic agent(s) and a rate controlling polymer(s).
  • a formulation according to the present invention may comprise additional ingredients such as one or more further active drug compound(s) and/or one or more pharmaceutically acceptable excipients as conventionally used, such as for instance diluents, e.g. lactose, , mannitol, starch; binders, e.g. polyvinyl pyrrolidone (PVP),; lubricants/glidants.e.g. magnesium stearate, talc, stearic acid, colloidal sodium dioxide; and also flavoring agents, taste masking agents, colouring agents, pigments, and preservatives.
  • diluents e.g. lactose, , mannitol, starch
  • binders e.g. polyvinyl pyrrolidone (PVP),
  • lubricants/glidants e.g. magnesium stearate, talc, stearic acid, colloidal sodium dioxide
  • flavoring agents taste masking agents, colouring
  • the controlled release formulations of the present invention are particularly suitable for oral administration.
  • Any orally administrable dosage form is contemplated by the present invention, in particular a tablet, a capsule, a pellet, or a sachet form.
  • the dosage form may be prepared according to conventional methods. For instance methods for the preparation of tablets or capsules may include direct compression, dry granulation, wet granulation. For dry granulation processes one suitable method of granule formation is compaction.
  • the controlled release formulation is in the form a tablet or capsule.
  • a tablet according to the present invention may be uncoated or coated, e.g. by a film or other conventional coating, using known methods.
  • the formulation is a once daily administrable formulation, e.g. a tablet for once daily administration.
  • a unit dosage form of a formulation according to the present invention may comprise an amount of cefuroxime axetil as conventional.
  • the pharmaceutical formulations according to the present invention provide controlled release of cefuroxime axetil.
  • the present invention is further illustrated by the following non-limiting examples.
  • cefuroxime axetil, Mg. Stearate, Avicel and sodium chloride are mixed and compressed into tablet form using a 16 mm round punch.
  • the resulting tablets are then passed through a sieve number 16 to get granules.
  • the granules are then lubricated with the remaining ingredients.
  • the lubricated material is compressed into tablets using a 19X9 mm caplet shape punch.
  • cefuroxime axetil, Sodium chloride and Avicel are mixed and compacted using roller compactor.
  • Compacted ribbons passed through a sieve number 16 to get granules.
  • the granules are then mixed with the remaining ingredients.
  • the mixed material is compressed into tablets using a 19 X 9 mm caplet shape punch.
  • Dissolution medium USP II; 0.1 N HCL; 100 rpm Time (Hrs) % of drug release 1 6 2 13 4 26 6 36 8 43 10 49 12 52 16 57
  • cefuroxime axetil, Sodium chloride and Avicel are mixed and compacted using roller compactor.
  • Compacted ribbons passed through a sieve number 16 to get granules.
  • the granules are then mixed with the remaining ingredients.
  • the mixed material is compressed into tablets using a 19X9 mm caplet shape punch.
  • Dissolution medium USP II; 0.1 N HCL; 100 rpm Time (Hrs) % of drug release 1 13 2 46 4 73 6 81 8 83 10 84
  • cefuroxime axetil, Mg. Stearate, and Avicel are mixed and compressed into tablet form using a 16 mm round punch.
  • the resulting tablets are then passed through a sieve number 16 to get granules.
  • the granules are then lubricated with the remaining ingredients.
  • the lubricated material is compressed into tablets using a 19X9 mm caplet shape punch.
  • Dissolution medium USP II; Phosphate buffer pH 6.8; 50 rpm
  • cefuroxime axetil, Mg. Stearate, Avicel and Methocel are mixed and compressed into tablet form using a 16 mm round punch.
  • the resulting tablets are then passed through a sieve number 16 to get granules.
  • the granules are then lubricated with the remaining ingredients.
  • the lubricated material is compressed into tablets using a 19X9 mm caplet shape punch.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Cephalosporin Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques de l'ester de I-acétoxyéthyle du composé antibiotique céfuroxime, connu sous le nom de céfuroxime axétil. L'invention concerne plus particulièrement aux formulations de céfuroxime axétil à libération contrôlée qui contiennent un ou plusieurs agents hydrophiles hydrosolubles.
PCT/EP2005/000322 2004-01-16 2005-01-14 Compositions pharmaceutiques a liberation controlee WO2005067895A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0400971A GB0400971D0 (en) 2004-01-16 2004-01-16 Pharmaceutical compositions
GB0400971.8 2004-01-16

Publications (1)

Publication Number Publication Date
WO2005067895A1 true WO2005067895A1 (fr) 2005-07-28

Family

ID=31726296

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/000322 WO2005067895A1 (fr) 2004-01-16 2005-01-14 Compositions pharmaceutiques a liberation controlee

Country Status (2)

Country Link
GB (1) GB0400971D0 (fr)
WO (1) WO2005067895A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009026725A1 (fr) * 2007-08-31 2009-03-05 Noveko Inc. Compositions antimicrobiennes et fibres incorporant de telles compositions
US8905034B2 (en) 2010-11-05 2014-12-09 Salutaris Llp Ergonomic protective air filtration devices and methods for manufacturing the same

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999062559A1 (fr) * 1998-05-29 1999-12-09 Bernard Charles Sherman Comprimes pharmaceutiques comprenant du cefuroxime axetil
WO2000056286A1 (fr) * 1999-03-19 2000-09-28 Ranbaxy Laboratories Limited Procede de preparation d'une forme posologique orale biodisponible de cefuroxime axetil
WO2002036126A1 (fr) * 2000-10-30 2002-05-10 Lupin Limited Composition de cefuroxime axetil a liberation lente et a desintegration rapide
US20020136764A1 (en) * 2000-02-24 2002-09-26 Rudnic Edward M. Antibiotic product, use and formulation thereof
US6534494B1 (en) * 1997-09-29 2003-03-18 Ranbaxy Laboratories Limited Process for the preparation of cefuroxime axetil in an amorphous form
WO2004019901A2 (fr) * 2002-08-30 2004-03-11 Orchid Chemicals & Pharmaceuticals Ltd. Composition pharmaceutique a liberation prolongee

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6534494B1 (en) * 1997-09-29 2003-03-18 Ranbaxy Laboratories Limited Process for the preparation of cefuroxime axetil in an amorphous form
WO1999062559A1 (fr) * 1998-05-29 1999-12-09 Bernard Charles Sherman Comprimes pharmaceutiques comprenant du cefuroxime axetil
WO2000056286A1 (fr) * 1999-03-19 2000-09-28 Ranbaxy Laboratories Limited Procede de preparation d'une forme posologique orale biodisponible de cefuroxime axetil
US20020136764A1 (en) * 2000-02-24 2002-09-26 Rudnic Edward M. Antibiotic product, use and formulation thereof
WO2002036126A1 (fr) * 2000-10-30 2002-05-10 Lupin Limited Composition de cefuroxime axetil a liberation lente et a desintegration rapide
WO2004019901A2 (fr) * 2002-08-30 2004-03-11 Orchid Chemicals & Pharmaceuticals Ltd. Composition pharmaceutique a liberation prolongee

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009026725A1 (fr) * 2007-08-31 2009-03-05 Noveko Inc. Compositions antimicrobiennes et fibres incorporant de telles compositions
US8905034B2 (en) 2010-11-05 2014-12-09 Salutaris Llp Ergonomic protective air filtration devices and methods for manufacturing the same

Also Published As

Publication number Publication date
GB0400971D0 (en) 2004-02-18

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