WO2005102289A1 - Formulation a liberation prolongee de clarithromycine - Google Patents

Formulation a liberation prolongee de clarithromycine Download PDF

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Publication number
WO2005102289A1
WO2005102289A1 PCT/IN2005/000085 IN2005000085W WO2005102289A1 WO 2005102289 A1 WO2005102289 A1 WO 2005102289A1 IN 2005000085 W IN2005000085 W IN 2005000085W WO 2005102289 A1 WO2005102289 A1 WO 2005102289A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
extended release
pharmaceutically acceptable
composition according
erythromycin
Prior art date
Application number
PCT/IN2005/000085
Other languages
English (en)
Inventor
Suryakumar Jayanthi
Vineeth Raghavan
Nilesh Bhandari
Himadri Sen
Original Assignee
Lupin Limited
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 Lupin Limited filed Critical Lupin Limited
Priority to EP05764065A priority Critical patent/EP1732518A1/fr
Priority to AU2005235237A priority patent/AU2005235237A1/en
Priority to MXPA06010805A priority patent/MXPA06010805A/es
Priority to BRPI0508743-0A priority patent/BRPI0508743A/pt
Publication of WO2005102289A1 publication Critical patent/WO2005102289A1/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
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to extended release pharmaceutical compositions of erythromycin or derivatives thereof for once daily administration.
  • Erythromycin and derivatives are known for their anti-bacterial activity against a number of micro-organisms and are typically administered as immediate release (IR) compositions, two or three times a day, for a regimen of 10 to 14 days.
  • IR immediate release
  • 6-O-methylerythromycin A (Clarithromycin), which has been disclosed in US patent No. 4,331,803. It is currently marketed by Abbott as an immediate release formulation, for at least twice daily administration. Abbott is also marketing controlled release composition of Clarithromycin 500 mg under the brand "Biaxin XL".
  • Literature discloses various approaches for therapeutic dosage forms, which are designed to deliver the drug at an extended rate to the gastrointestinal tract.
  • U.S. Patent 4,842,866 discloses the development of a controlled release formulation of erythromycin derivatives using an alginate matrix comprising a water-soluble alginate and a complex salt of alginic acid, having one cation that yields a soluble alginate salt and another cation that alone yields an insoluble alginate salt.
  • U.S. Patent 5,705,190 claims formulations using soluble alginate, a complex salt of alginic acid and an organic carboxylic acid.
  • the said patent discloses compositions containing equimolar quantities of citric acid and clarithromycin.
  • US patents 6,010,718, and 6,551,616 disclose formulations of extended release clarithromycin containing 5 to 50% w/w of pharmaceutically acceptable polymer.
  • the specification and examples of this patent disclose preferred formulations containing 10%-
  • US patent application 2003/0175341 discloses controlled release formulations containing about 0.1% to about 4.5% of one or more cellulosic ether rate controlling polymers.
  • PCT application WO 03/082241 discloses clarithromycin formulations having improved bioavailability, using micronized drug.
  • the patent exemplifies formulations of extended release clarithromycin containing the drug of particle size less than 35 microns. Improved dissolution relative to un-micronized drug is documented in the said patent. However, the formulation as disclosed in the patent application does not show significant improvement in bioavailability.
  • U.S. Pat. No. 4,389,393 describes sustained release therapeutic composition using less than about one third of the weight of the solid unit dosage form, of hydroxypropyl methylcellulose or a mixture of hydroxypropyl methylcellulose with certain other rate controlling polymers.
  • the inventors disclose that they have been able to achieve sustained release from solid dosage forms containing as little as about 5 to about 30 weight percent of these hydroxypropyl methylcelluloses. All the examples disclose compositions containing 9% or more of the rate-controlling polymer.
  • compositions prepared using polymers in the range of about 50% to about 65% showed pharmacokinetic profile similar to the innovator, which has lower polymer content.
  • the object of the present invention is to provide a pharmaceutical composition for extended release of erythromycin or its derivatives for once daily administration comprising about 50% to about 65% by weight of pharmaceutically acceptable polymers.
  • Another object of the invention is to provide a process for preparing extended release composition of erythromycin or its derivatives comprising mixing the drug with about 50% to about 65% by weight of one or more than one of pharmaceutically acceptable polymers, granulating the blend by wet or dry means, followed by either filling the granules into capsules, sachets or compressing them into tablets.
  • Yet another object of the present invention is to provide a pharmaceutical composition for extended release of Clarithromycin comprising from about 50% to about 65% of pharmaceutically acceptable polymers, wherein the T/R ratio of the geometric mean of Cmax and AUC are within acceptable limit (80-125%) with respect to the currently marketed extended release Clarithromycin formulation marketed under the trade name Biaxin XL.
  • an extended release formulation of erythromycin or its derivatives suitable for once daily oral administration comprising about 50% to about 65% by weight of pharmaceutically acceptable polymers or combinations thereof.
  • the invention provides for an extended release formulation of erythromycin or derivatives thereof, comprising erythromycin or derivatives thereof, pharmaceutically acceptable polymers in the range of about 50% to about 65% by weight, in addition to other pharmaceutically acceptable excipients
  • the extended release formulation of the invention is prepared by following the processes of wet or dry granulation, filling the granules into capsules, sachets or compressing into tablets.
  • Erythromycin or derivatives used according to the present invention comprise about 10% to about 40% of the total weight of the formulation.
  • the pharmaceutically acceptable polymers are present in the range of about 50% to about 65% by weight.
  • the pharmaceutically acceptable polymers according to the present invention may be selected from group of polyvinyl pyrrolidine, celluloses, polyvinyl pyrrolidone/polyvinyl acetate copolymers, polyethylene oxide polymers, acrylic acid polymers, methacrylic acid copolymers, natural gums, and derivatives and mixtures thereof.
  • Celluloses used in accordance with the present invention include hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethylcellulose, methylcellulose and the like.
  • the viscosity of the polymers may be in the range of 5 to 200 cps.
  • Polyvinyl pyrrolidone/polyvinyl acetate copolymers according to the present invention may be such as available under the brand name Kollidon SR (BASF).
  • Polyethylene oxide polymers are sold by Union Carbide.
  • Natural gums according to the present invention include Xanthan gum, Locust bean gum, guar gum, gum karaya, alginates and the like.
  • Acrylic acid polymers according to the present invention may be such as available under the brand name carbopol (B.F. Goodrich, USA).
  • composition may contain pharmaceutically acceptable excipients such as buffering agents, binders, lubricants and fillers.
  • Buffering agents may be selected from the groups comprising alkali and alkaline earth metal phosphates, citrates, succinates, and the like.
  • Fillers according to the present invention may be selected from amongst those conventionally used in the art such as lactose, starches, glucose, sucrose, mannitol, silicic acid and mixtures thereof.
  • composition according to the present invention may also contain pharmaceutically acceptable lubricants such as those selected from amongst talc, calcium stearate, magnesium stearate, polyethylene glycol, silicon dioxide, sodium stearyl fumarate and the like.
  • pharmaceutically acceptable lubricants such as those selected from amongst talc, calcium stearate, magnesium stearate, polyethylene glycol, silicon dioxide, sodium stearyl fumarate and the like.
  • the release profile of the product is evaluated using USP apparatus Type 1 (basket), at 100 rpm in 900 ml. Medium for 0 to 2h, pH 3.5 acetate buffer. The medium was then changed to pH 6.8 phosphate buffer, for the next 12 hours.
  • Example 1 i) Clarithromycin 38.46 % ii) Hydroxypropyl Methylcellulose lOOcps 7.00 % iii) Hydroxypropyl Methylcellulose 5cps 48.00 % iv) Lactose 4.23 % v) Talc 1.54 % vi) Magnesium Stearate 0.77 % vii) Water qs
  • Example 2 i) Clarithromycin 38.46 % ii) Hydroxypropyl Methylcellulose 5cps 50.00 % iii) Kollidone SR 5.00 % iv) Lactose 4,23 % v) Talc 1.54 % vi) Magnesium Stearate 0.77 % vii) Water qs Procedure : The drug and excipients were blended and granulated with water. The granules were dried, sized, lubricated and compressed into tablets of suitable size and hardness.
  • Example 3 i) Clarithromycin 38.46 % ii)Hydroxypropyl Methylcellulose 5cps 46.50 % iii) Hydroxypropyl Methylcellulose lOOcps 7.00 % iv) Sodium alginate (Keltone LVCR) 1.50 % v) Lactose 4.23 % vi) Talc 1.54 % vii) Magnesium Stearate 0.77 % viii) Water qs
  • Example 4 i) Clarithromycin 38.46 % ii) Hydroxypropyl Methylcellulose lOOcps 10.00 % iii) Hydroxypropyl Methylcellulose 5cps 45.00 % iv) Lactose 4.23 % v) Talc 1.54 % vi) Magnesium Stearate 0.77 % vii) Water qs
  • Example 6 i) Clarithromycin 35.89 % ii)Hydroxypropyl Methylcellulose 5cps 48.50 % iii) Hydroxypropyl Methylcellulose lOOcps 7.00 % ( Methocel KlOO LN) iv) Sodium alginate (Keltone LNCR) 1.50 % v) Xanthan Gum 1.00 % vi) Lactose 3.95 % vii) Talc 1.44 % viii) Magnesium Stearate 0.72 % ix) Water qs
  • Formulation prepared according to one of the preceeding examples was subjected to a bioequivalence study against the extended release formulation of Clarithromycin marketed under the name Biaxin XL TM in the US.
  • the T/R ratio of geometric mean of Cmax and AUC was within acceptable limits (80%-125%) as shown in Table II.

Abstract

La présente invention concerne une composition pharmaceutique permettant la libération prolongée de d'érythromycine ou d'un dérivé de celle-ci. La composition comprend une quantité efficace d'un point de vue pharmaceutique, d'un médicament et d'environ 50 % à environ 65 % en poids d'un ou de plusieurs polymères acceptables d'un point de vue pharmaceutique. Les polymères acceptables d'un point de vue pharmaceutique, sont choisis dans le groupe comprenant polyvinyl pyrrolidine, hydroxypropyl cellulose, hydroxypropylméthyl cellulose, méthylcellulose, éthyl cellulose, copolymères de polyvinyl pyrrolidone/polyvinyl acétate, polymères de polyéthylène oxyde, polymères d'acide acrylique, copolymères d'acide méthacrylique, gommes naturelles et dérivés et mélanges de ceux-ci.
PCT/IN2005/000085 2004-03-24 2005-03-17 Formulation a liberation prolongee de clarithromycine WO2005102289A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP05764065A EP1732518A1 (fr) 2004-03-24 2005-03-17 Formulation a liberation prolongee de clarithromycine
AU2005235237A AU2005235237A1 (en) 2004-03-24 2005-03-17 Clarithromycin extended release formulation
MXPA06010805A MXPA06010805A (es) 2004-03-24 2005-03-17 Formulacion de claritromicina de libracion prolongada.
BRPI0508743-0A BRPI0508743A (pt) 2004-03-24 2005-03-17 composição farmacêutica com uma liberação estendida de eritromicina ou um derivado da mesma, método para o uso de uma composição farmacêutica e processo para a preparação de uma composição farmacêutica

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN356/MUM/2004 2004-03-24
IN356MU2004 2004-03-24

Publications (1)

Publication Number Publication Date
WO2005102289A1 true WO2005102289A1 (fr) 2005-11-03

Family

ID=34979410

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2005/000085 WO2005102289A1 (fr) 2004-03-24 2005-03-17 Formulation a liberation prolongee de clarithromycine

Country Status (5)

Country Link
EP (1) EP1732518A1 (fr)
AU (1) AU2005235237A1 (fr)
BR (1) BRPI0508743A (fr)
MX (1) MXPA06010805A (fr)
WO (1) WO2005102289A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1638529A2 (fr) * 2003-06-16 2006-03-29 ANDRX Pharmaceuticals, LLC. Composition orale a liberation prolongee
WO2008114143A1 (fr) * 2007-03-22 2008-09-25 Aurobindo Pharma Limited Formulations à libération prolongée d'un antibiotique macrolide
EP2005946A1 (fr) * 2006-04-12 2008-12-24 Nippon Soda Co., Ltd. Méthode pour produire un comprimé à libération retardée
JP2009517420A (ja) * 2005-11-30 2009-04-30 メルツ・ファルマ・ゲゼルシヤフト・ミト・ベシュレンクテル・ハフツング・ウント・コンパニー・コマンデイトゲゼルシヤフト・アウフ・アクティーン ネラメキサン放出調節マトリックス錠

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0312340A1 (fr) * 1987-10-12 1989-04-19 Biosat Limited Utilisation de carbomère dans des compositions à libération contrôlée pour augmenter le taux de libération des substances pharmacologiquement actives peu solubles
US6010718A (en) * 1997-04-11 2000-01-04 Abbott Laboratories Extended release formulations of erythromycin derivatives
WO2000048607A1 (fr) * 1999-02-19 2000-08-24 LEK, tovarna farmacevtskih in kemičnih izdelkov, d.d. Matrice directement compressible pour liberation controlee de doses quotidiennes uniques de clarithromycine
EP1302205A1 (fr) * 2001-10-01 2003-04-16 Ind-Swift Limited Composition pharmaceutique à libération contrôlée comprenant citrate de macrolide
WO2004112711A2 (fr) * 2003-06-16 2004-12-29 Andrx Pharmaceuticals, Llc Composition orale a liberation prolongee
US20050136107A1 (en) * 2003-12-22 2005-06-23 Patel Mahendra R. Extended release antibiotic composition

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0312340A1 (fr) * 1987-10-12 1989-04-19 Biosat Limited Utilisation de carbomère dans des compositions à libération contrôlée pour augmenter le taux de libération des substances pharmacologiquement actives peu solubles
US6010718A (en) * 1997-04-11 2000-01-04 Abbott Laboratories Extended release formulations of erythromycin derivatives
WO2000048607A1 (fr) * 1999-02-19 2000-08-24 LEK, tovarna farmacevtskih in kemičnih izdelkov, d.d. Matrice directement compressible pour liberation controlee de doses quotidiennes uniques de clarithromycine
EP1302205A1 (fr) * 2001-10-01 2003-04-16 Ind-Swift Limited Composition pharmaceutique à libération contrôlée comprenant citrate de macrolide
WO2004112711A2 (fr) * 2003-06-16 2004-12-29 Andrx Pharmaceuticals, Llc Composition orale a liberation prolongee
US20050136107A1 (en) * 2003-12-22 2005-06-23 Patel Mahendra R. Extended release antibiotic composition

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1638529A2 (fr) * 2003-06-16 2006-03-29 ANDRX Pharmaceuticals, LLC. Composition orale a liberation prolongee
EP1638529B1 (fr) * 2003-06-16 2016-08-10 ANDRX Pharmaceuticals, LLC. Composition orale a liberation prolongee
JP2009517420A (ja) * 2005-11-30 2009-04-30 メルツ・ファルマ・ゲゼルシヤフト・ミト・ベシュレンクテル・ハフツング・ウント・コンパニー・コマンデイトゲゼルシヤフト・アウフ・アクティーン ネラメキサン放出調節マトリックス錠
JP2013136620A (ja) * 2005-11-30 2013-07-11 Merz Pharma Gmbh & Co Kgaa ネラメキサン放出調節マトリックス錠
EP2005946A1 (fr) * 2006-04-12 2008-12-24 Nippon Soda Co., Ltd. Méthode pour produire un comprimé à libération retardée
EP2005946A4 (fr) * 2006-04-12 2011-03-02 Nippon Soda Co Méthode pour produire un comprimé à libération retardée
US8617596B2 (en) 2006-04-12 2013-12-31 Nippon Soda Co., Ltd. Sustained-release tablet production process
WO2008114143A1 (fr) * 2007-03-22 2008-09-25 Aurobindo Pharma Limited Formulations à libération prolongée d'un antibiotique macrolide

Also Published As

Publication number Publication date
AU2005235237A1 (en) 2005-11-03
MXPA06010805A (es) 2006-12-19
BRPI0508743A (pt) 2008-01-22
EP1732518A1 (fr) 2006-12-20

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