WO2008114143A1 - Formulations à libération prolongée d'un antibiotique macrolide - Google Patents

Formulations à libération prolongée d'un antibiotique macrolide Download PDF

Info

Publication number
WO2008114143A1
WO2008114143A1 PCT/IB2008/000800 IB2008000800W WO2008114143A1 WO 2008114143 A1 WO2008114143 A1 WO 2008114143A1 IB 2008000800 W IB2008000800 W IB 2008000800W WO 2008114143 A1 WO2008114143 A1 WO 2008114143A1
Authority
WO
WIPO (PCT)
Prior art keywords
extended release
weight
polymer
eudragit
release formulation
Prior art date
Application number
PCT/IB2008/000800
Other languages
English (en)
Inventor
Vikas Yande
Shailesh Kulkarni
Imran Alana
Srinivas Nimbalkar
Ravi Naidu Peddi
Sivakumaran Meenakshisunderam
Original Assignee
Aurobindo Pharma 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 Aurobindo Pharma Limited filed Critical Aurobindo Pharma Limited
Publication of WO2008114143A1 publication Critical patent/WO2008114143A1/fr

Links

Classifications

    • 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
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/2013—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
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to an extended release formulation of macrolide antibiotic. More particularly, the present invention relates to an extended release formulation of erythromycin derivatives.
  • the present invention also relates to a process for the preparation of extended release formulation containing erythromycin derivatives.
  • Erythromycin derivatives exhibit broad spectrum antibacterial activity against gram-positive and gram-negative microorganisms. These erythromycin derivatives include azithromycin, clarithromycin and roxithromycin.
  • erythromycin derivatives available in the market for the treatment of bacterial infections include azithromycin marketed under the trade name Zithromax ® , clarithromycin marketed under the trade name Biaxin ® .
  • clarithromycin is 6-0-methylerythromycin, which is commercially available as granules for oral suspension, film coated tablets and extended release tablets.
  • azithromycin is N-methyl-11-aza-lO-deoxo-lO-dihydro- erythromycin A which is commercially available as tablets, suspension, extended release suspension and injection.
  • clarithromycin extended release tablets contain 500 mg of clarithromycin as active ingredient and excipients such as cellulosic polymers, lactose monohydrate, magnesium stearate, propylene glycol, sorbic acid, sorbitan monooleate, talc, titanium dioxide, D&C Yellow No. 10 and vanillin.
  • U.S. 5,705,190 discloses controlled release compositions comprising poorly soluble basic drug, a water-soluble alginate salt, a complex salt of alginic acid and an organic carboxylic acid to facilitate dissolution of the basic drug.
  • U.S. 6,010,718, US 6,551,616 and US 6,872,407 disclose extended release pharmaceutical composition comprising an erythromycin derivative and from about 5 to about 50% by weight of a pharmaceutically acceptable polymer, wherein the polymer is selected from the group consisting of polyvinylpyrrolidine, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, vinylacetate/crotonicacid copolymers, methacrylic acid copolymers, maleic anhydride/methyl vinyl ether copolymers and derivatives and mixtures.
  • U.S. 6,068,859 discloses a controlled release dosage form comprising azithromycin and a pharmaceutically acceptable carrier wherein azithromycin is embedded in a polymeric matrix which releases azithromycin by eroding wherein the polymer is selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose, poly( ethylene oxide) and polyacrylic acid.
  • U.S. 6,642,276 discloses controlled release formulation comprising, a macrolide citrate salt; at least one hydrophilic polymer; a binder, a filler; and a lubricant.
  • the preferred range of hydrophilic polymer is from about 5-15% by weight.
  • This patent further discloses that the use of macrolide citrate salt overcome the problem of poor solubility, pH-dependent solubility and irreproducible bioavailability.
  • U.S. 7,037,523 discloses controlled release composition
  • the preferred range of water insoluble polymer is from about 10 to about 40% in addition to other excipients.
  • the preferable optimizing agent is a combination comprising a polymer of methacrylic acid and methyl methacrylate and a compound selected from the group consisting of lactose, dicalcium phosphate and tricalcium phosphate or a mixture thereof present in the range of 10 to about 90%.
  • U.S. 7,063,862 discloses composition comprising clarithromycin, from about 0.1% to about 4.9% by weight of a swellable and water-soluble pharmaceutically acceptable polymer; and from about 0.1% to about 30% by weight of a pharmaceutically acceptable acid. This patent further discloses that the pharmaceutically acceptable acid in the pharmaceutical composition enhances the gelling process of the pharmaceutically acceptable polymer to achieve the zero- order drug release profile.
  • U.S. 2004/0043073 discloses controlled release oral dosage form comprising a matrix comprising a drug having a pH dependent solubility; at least one wax material in an effective amount to provide a controlled release of said drug for at least 12 hours in an environment of use; and at least one pH modifying agent.
  • U.S. 2005/0136107 discloses an extended-release antibiotic composition comprising at least one antibiotic, and greater than 50 weight percent, based on the total weight of the composition, of a polymer component, wherein said polymer component comprises at least one pharmaceutically acceptable hydrophilic polymer, and said polymer component has a viscosity of less than about 50 cps.
  • U.S. 2006/0193908 discloses extended release composition comprising a macrolide antibiotic; one or more surfactants and one or more non-lipophilic, non- polymeric excipients.
  • U.S. 2007/0015719 discloses stable nanoparticulate composition comprising particles of clarithromycin, having an effective average particle size of less than about 2000 nm and at least one surface stabilizer.
  • EP 1 757 277 Al discloses an oral preparation comprising a complex obtained by dissolving clarithromycin and gastric high-molecular compound in a low melting point substance and then coating the said complex with insoluble high- molecular compound and a disintegrant.
  • WO 2007/122474 discloses extended release pharmaceutical composition
  • the first layer comprises of a) a therapeutically effective amount of clarithromycin or a pharmaceutically acceptable salt, solvate or derivatives thereof along with at least one rate controlling hydrophilic polymer having high viscosity and other suitable pharmaceutical excipients and b) the second layer comprises of a therapeutically effective amount of clarithromycin or a pharmaceutically acceptable salt, solvate or derivatives thereof along with at least one rate controlling hydrophilic polymer having low viscosity and other suitable pharmaceutical excipients.
  • the main objective of the present invention is to prQvide extended release formulation of erythromycin derivative.
  • Yet another objective of the present invention is to provide an extended release formulation of erythromycin derivative in such a way that it will comply with the reference product in terms of in vivo parameters like C max , t max , AUC and in vitro parameters like dissolution etc.
  • Yet another objective of the present invention is to provide process for the preparation of an extended release formulation of erythromycin derivative.
  • the main embodiment of the present invention is to provide an extended release formulation comprising erythromycin derivative and controlled release polymer, wherein the polymer is selected from:
  • erythromycin derivative include azithromycin, clarithromycin and roxithromycin.
  • the extended release formulation further comprises one or more excipients selected from diluents, glidants and lubricants.
  • the extended release formulation comprises at least 50% by weight of erythromycin derivative and a combination of 0.1 to 10% by weight of water insoluble methacrylic acid copolymer and/or methacrylate ester copolymer and hydrophilic polymer wherein the ratio of water insoluble methacrylic acid copolymer and hydrophilic polymer is about 1 :3 to about 3: 1 by weight.
  • water insoluble methacrylic acid copolymer and/or methacrylate ester copolymer include Eudragit RS PO, Eudragit RS 100, Eudragit RS 12.5, Eudragit NE 30 D and Eudragit RS 30D which is a copolymer of Poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride).
  • the amount of water insoluble methacrylic acid copolymer is in the range of about 0.1 to about 10% w/w, preferably about 0.1 to about 6% w/w.
  • Suitable hydrophilic polymer includes polyethylene oxide, carbomer, vinyl acetate copolymers, carboxymethylcellulose sodium, povidone and the like.
  • the extended release formulation of the present invention is essentially free of organic acid, which enhances the gelling process of the polymer to achieve the zero-order drug release profile.
  • Suitable diluents of the present invention include sucrose, calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, mannitol, starch, pregelatinised starch, sorbitol and the like or combination thereof.
  • the amount of diluent may range from about 10% to 40% by weight.
  • Suitable binders of the present invention include povidone, xanthan gum, gelatin, starch, pregelatinized starch and the like.
  • Suitable glidants of the present invention include calcium silicate, magnesium carbonate, magnesium oxide, magnesium silicate, talc, silicon dioxide, starch and the like.
  • Suitable lubricants of the present invention include sodium stearyl fumarate, magnesium stearate, calcium stearate, hydrogenated vegetable oil, stearic acid, glyceryl behenate, talc, carnauba wax and the like.
  • the extended formulation of the present invention may optionally contain sodium dihydrogen phosphate or sodium hydrogen phosphate.
  • the solubility of clarithromycin decreases as pH increases to pH 5.0 and above. Small quantities of sodium dihydrogen phosphate or sodium hydrogen phosphate can be used to modify the release of clarithromycin formulations.
  • the preferable extended release formulation according to present invention comprise at least 50% by weight of clarithromycin, 0.1 to 10% by weight of water insoluble methacrylic acid copolymer and/or methacrylate ester copolymer selected from Eudragit RS PO, Eudragit NE 30 D and Eudragit RS 3OD; 10% to 40% by weight of diluent selected from lactose monohydrate, microcrystalline cellulose and dibasic calcium phosphate or combination thereof.
  • the preferable extended release formulation according to present invention comprise at least 50% by weight of clarithromycin, 0.1 " to 5% of hydrophilic polymer selected from polyethylene oxide, carbomer , carboxymethylcellulose sodium and povidone; 10% to 40% by weight of diluent selected from lactose monohydrate, microcrystalline cellulose and dibasic calcium phosphate or combination thereof.
  • the preferable extended release formulation according to present invention comprise at least 50% by weight of clarithromycin, 0.1 to 10% by weight of water insoluble methacrylic acid copolymer and/or methacrylate ester copolymer selected from Eudragit RS PO, Eudragit NE 30 D and Eudragit RS 30D; 0.1 to 5% of hydrophilic polymer selected from polyethylene oxide, carbomer, carboxymethylcellulose sodium and povidone; 10% to 40% by weight of diluent selected from lactose monohydrate, microcrystalline cellulose and dibasic calcium phosphate or combination thereof.
  • the extended release formulations are prepared by granulation technique such as dry or wet granulation or direct compression.
  • the dosage forms of the extended release formulations include tablets or capsules.
  • the tablets may be uncoated or optionally coated.
  • the film coating composition comprises a solution / suspension of film coating polymers and one or more excipients such as lactose, titanium dioxide, solubilizing agent and antisticking agent.
  • Suitable film coating polymers used according to the present invention are selected from ethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose and the like or mixtures thereof.
  • the solubilizing agent of the present invention may be selected from anionic or non-ionic surfactants such as sodium lauryl sulphate, polyethylene-propylene glycol copolymer (poloxamer), polyoxyethylene stearates (Macrogol-stearate), poly sorbates, propylene glycol, and the like or mixtures thereof.
  • anionic or non-ionic surfactants such as sodium lauryl sulphate, polyethylene-propylene glycol copolymer (poloxamer), polyoxyethylene stearates (Macrogol-stearate), poly sorbates, propylene glycol, and the like or mixtures thereof.
  • Suitable anti-sticking agents used according to the present invention are selected from talc, magnesium stearate and the like or a mixture thereof.
  • step (iii) mixtures thereof, wherein the polymer is not cellulose ether when used alone, comprises the steps of: i) dry blending erythromycin derivative and optionally controlled release polymer with one or more intra granular excipients, ii) granulating the blend of step (i) with a solvent and optionally a binder or polymer, iii) drying the granules obtained in step (ii), iv) blending the dried granules of step (iii) with one or more extra granular excipients and optionally controlled release polymer, v) lubricating the blend of step (iv), v) compressing the blend of step (v) into tablets or filled into capsules and vi) finally coating the tablets of step (vi) with film forming materials.
  • Suitable solvents used for granulation are selected from water, isopropyl alcohol, ethanol, acetone, methylene chloride and the like or mixture thereof.
  • the present invention also provides a method of treating acute maxillary sinusitis, pharyngitis / tonsillitis, disseminated mycobacterial infections, acute bacterial exacerbation of chronic bronchitis and/or community-acquired pneumonia by administering extended release formulation prepared according to present invention.
  • Example 1 (Clarithromycin extended release tablets with water insoluble methacrylic acid copolymer)
  • clarithromycin extended release tablets of example 1 & 2 The processing steps involved in manufacturing clarithromycin extended release tablets of example 1 & 2 are given below: i) clarithromycin and microcrystalline cellulose were blended, ii) a solution/dispersion of eudragit in isopropyl alcohol and/or water was prepared, iii) granulated the blended material of step (i) with a solution of step (ii) and dried the granulated mass, iv) granules of step (iii) were blended with microcrystalline cellulose, v) lubricated the granules of step (iv), vi) compressed the blend of step (v) into tablets and vii) tablets of step (vi) were coated with a solution / suspension of opadry in water.
  • clarithromycin extended release tablets of example 3 & 4 The processing steps involved in manufacturing clarithromycin extended release tablets of example 3 & 4 are given below: i) clarithromycin, lactose monohydrate and microcrystalline cellulose were blended, ii) granulated the blended material of step (i) with eudragit dispersion and the granulated mass was dried, iii) granules of step (ii) were blended with colloidal silicon dioxide, iv) lubricated the granules of step (iii), v) compressed the blend of step (iv) into tablets and vi) tablets of step (v) were coated with a solution / suspension of opadry in water.
  • clarithromycin extended release tablets of example 5 & 6 The processing steps involved in manufacturing clarithromycin extended release tablets of example 5 & 6 are given below: i) clarithromycin, lactose monohydrate microcrystalline cellulose and eudragit were blended, ii) granulated the blended material of step (i) with water and the granulated mass was dried, iii) granules of step (ii) were blended with colloidal silicon dioxide, iv) lubricated the granules of step (iii), v) compressed the blend of step (iv) into tablets and vi) tablets of step (v) were coated with a solution / suspension of opadry in water.
  • Example 7 (Clarithromycin extended release tablets with water insoluble methacrylic acid copolymer and hydrophilic polymer)
  • clarithromycin extended release tablets disclosed in example 7 are given below: i) clarithromycin, lactose monohydrate, microcrystalline cellulose and polyethylene oxide were blended, ii) a dispersion of eudragit in water was prepared, iii) granulated the blended material of step (i) with a dispersion of step (ii) and dried the granulated mass, iv) granules of step (iii) were blended with colloidal silicon dioxide, v) lubricated the granules of step (iv), vi) compressed the blend of step (v) into tablets and vii) tablets of step ' (vi) were coated with a solution / suspension of opadry in water.
  • Example 12 (Clarithromycin extended release tablets with hydrophilic polymer)
  • Example 13 (Clarithromycin extended release tablets with hydrophilic polymer)
  • clarithromycin extended release tablets of example 12& 13 The processing steps involved in manufacturing clarithromycin extended release tablets of example 12& 13 are given below: i) clarithromycin, lactose monohydrate and microcrystalline cellulose were blended, ii) a solution of povidone in water was prepared, iii) granulated the blended material of step (i) with a solution of step (ii) and dried the granulated mass, iv) granules of step (iii) were blended with carbopol and colloidal silicon dioxide, v) lubricated the granules of step (iv), vi) compressed the blend of step (v) into tablets and vii) tablets of step (vi) were coated with a solution / suspension of opadry in water.
  • clarithromycin extended release tablets disclosed in example 14 are given below: i) clarithromycin, lactose monohydrate, microcrystalline cellulose and sodium hydrogen phosphate were blended, ii) a dispersion of eudragit in water was prepared, iii) granulated the blended material of step (i) with a dispersion of step (ii) and dried the granulated mass, iv) granules of step (iii) were blended with colloidal silicon dioxide, v) lubricated the granules of step (iv), vi) compressed the blend of step (v) into tablets and vii) tablets of step (vi) were coated with a solution / suspension of opadry in water.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention porte sur une formulation à libération prolongée d'un antibiotique macrolide. Plus particulièrement, la présente invention porte sur une formulation à libération prolongée de dérivés d'érythromycine. La présente invention porte également sur un procédé pour la préparation d'une formulation à libération prolongée contenant des dérivés d'érythromycine.
PCT/IB2008/000800 2007-03-22 2008-03-17 Formulations à libération prolongée d'un antibiotique macrolide WO2008114143A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN584CH2007 2007-03-22
IN584/CHE/2007 2007-03-22
IN2578CH2007 2007-11-09
IN2578/CHE/2007 2007-11-09

Publications (1)

Publication Number Publication Date
WO2008114143A1 true WO2008114143A1 (fr) 2008-09-25

Family

ID=39671667

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2008/000800 WO2008114143A1 (fr) 2007-03-22 2008-03-17 Formulations à libération prolongée d'un antibiotique macrolide

Country Status (1)

Country Link
WO (1) WO2008114143A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030119760A1 (en) * 2001-11-02 2003-06-26 Javed Hussain Controlled release compositions for macrolide antimicrobial agents
WO2004056344A1 (fr) * 2002-12-23 2004-07-08 Sandoz Ag Preparation a liberation prolongee a base de clarithromycine
WO2004089340A1 (fr) * 2003-04-09 2004-10-21 Cmax Otimizacão De Resultados Sc Ltda Compositions pharmaceutiques, methode, et utilisation d'une formulation dans le traitement et la prevention d'infections associees a l'helicobacter pylori chez les mammiferes et les humains
US20050053658A1 (en) * 2003-09-09 2005-03-10 Venkatesh Gopi M. Extended release systems for macrolide antibiotics
WO2005079752A2 (fr) * 2004-02-11 2005-09-01 Rubicon Research Private Limited Compositions pharmaceutiques a liberation controlee presentant une meilleure biodisponibilite
WO2005082331A2 (fr) * 2004-02-26 2005-09-09 Ranbaxy Laboratories Limited Comprimes a liberation prolongee de clarithromycine
WO2005102289A1 (fr) * 2004-03-24 2005-11-03 Lupin Limited Formulation a liberation prolongee de clarithromycine

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030119760A1 (en) * 2001-11-02 2003-06-26 Javed Hussain Controlled release compositions for macrolide antimicrobial agents
WO2004056344A1 (fr) * 2002-12-23 2004-07-08 Sandoz Ag Preparation a liberation prolongee a base de clarithromycine
WO2004089340A1 (fr) * 2003-04-09 2004-10-21 Cmax Otimizacão De Resultados Sc Ltda Compositions pharmaceutiques, methode, et utilisation d'une formulation dans le traitement et la prevention d'infections associees a l'helicobacter pylori chez les mammiferes et les humains
US20050053658A1 (en) * 2003-09-09 2005-03-10 Venkatesh Gopi M. Extended release systems for macrolide antibiotics
WO2005079752A2 (fr) * 2004-02-11 2005-09-01 Rubicon Research Private Limited Compositions pharmaceutiques a liberation controlee presentant une meilleure biodisponibilite
WO2005082331A2 (fr) * 2004-02-26 2005-09-09 Ranbaxy Laboratories Limited Comprimes a liberation prolongee de clarithromycine
WO2005102289A1 (fr) * 2004-03-24 2005-11-03 Lupin Limited Formulation a liberation prolongee de clarithromycine

Similar Documents

Publication Publication Date Title
US20200000726A1 (en) Gastroresistant pharmaceutical formulations containing rifaximin
EP1318792B1 (fr) Composition a liberation prolongee contenant de la clarithromycine
JP7112333B2 (ja) 改善された薬物製剤
US20050053658A1 (en) Extended release systems for macrolide antibiotics
WO2017032908A1 (fr) Composition pharmaceutique comprenant du posaconazole amorphe
HU204194B (en) Process for producing instant and retard gemfibrosil compositions
CA2833115C (fr) Compositions pharmaceutiques de raltegravir, procedes de preparation et utilisation de celles-ci
US20140079779A1 (en) Modified Release Tranexamic Acid Formulation
AU2014237934B2 (en) Controlled release pharmaceutical dosage forms
US7037523B2 (en) Controlled release compositions for macrolide antimicrobial agents
US20100055177A1 (en) Modified release composition of levetiracetam and process for the preparation thereof
WO2022153330A1 (fr) Compositions pharmaceutiques comprenant de l'acalabrutinib
KR20220077094A (ko) 안정성 및 생체이용율이 개선된 올라파립 고체 분산체 조성물
KR100771426B1 (ko) 마이크로펠렛을 이용한 약물학적 조성물 및 그의 제조방법
US20120178810A1 (en) Extended release formulation of an antiepileptic agent
WO2008114143A1 (fr) Formulations à libération prolongée d'un antibiotique macrolide
JP7378393B2 (ja) 改善された薬物製剤
WO2013088274A1 (fr) Composition d'azithromycine amorphe anhydre dépourvue de dihydrate d'azithromycine
WO2005004919A2 (fr) Systemes de liberation prolongee destines a des antibiotiques macrolides
WO2007122474A2 (fr) Formulations à libération prolongée

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08737378

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08737378

Country of ref document: EP

Kind code of ref document: A1