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WO2011112160A1 - Comprimés de trimétazidine à libération lente - Google Patents

Comprimés de trimétazidine à libération lente Download PDF

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Publication number
WO2011112160A1
WO2011112160A1 PCT/TR2010/000173 TR2010000173W WO2011112160A1 WO 2011112160 A1 WO2011112160 A1 WO 2011112160A1 TR 2010000173 W TR2010000173 W TR 2010000173W WO 2011112160 A1 WO2011112160 A1 WO 2011112160A1
Authority
WO
WIPO (PCT)
Prior art keywords
extended release
trimetazidine
composition according
release tablet
tablet
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/TR2010/000173
Other languages
English (en)
Inventor
Abdullah Bulgur
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.)
ALI RAIF ILAC SANAYI VE TICARET AS
Original Assignee
ALI RAIF ILAC SANAYI VE TICARET AS
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 ALI RAIF ILAC SANAYI VE TICARET AS filed Critical ALI RAIF ILAC SANAYI VE TICARET AS
Publication of WO2011112160A1 publication Critical patent/WO2011112160A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K9/2031—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
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing

Definitions

  • Present invention is related to the controlled release form containing 1 -(2,3,4- trimethoxybenzyl) piperazine dihydrochloride and prepared by direct compressing using polyethylene oxide.
  • the formulation presents a stable release profile in the pH limit of gastrointestinal system and stabilized in terms of impurities.
  • Trimetazidine is a 1-(2,3,4-trimethoxybenzyl) piperazine compound, molecular formula of which is Ci 4 H 2 2 2 0 3 (Formula I). Its molecular weight is 266.34 and freely soluble in water, it has two pKa values at 4.32 and 8.95.
  • Trimetazidine prevents the reduction of intracellular ATP (Adenosintriphosphate) by protecting the energy metabolism of the cell exposed to hypoxia or ischemia.
  • intracellular ATP Adosintriphosphate
  • mechanism of ion pumps and intracellular entrance-exit of Na/K ions are arranged and cellular homeostasis is established. It is indicated in treatment of 'Angina pectoris'.
  • trimetazidine dihydrochloride 20 mg immediate release tablets and controlled release tablets containing 35 mg Trimetazidine. It is quickly absorbed and reaches maximum blood concentration in 1.8+0.7 h. Plasma elimination half life is about 6+1.4 hours. As it has a short plasma elimination half life, 20 mg preparation is applied 2 or 3 times daily to practically get relatively stable plasma levels. As the active substance is absorbed quickly, maximum plasma concentration is reached shortly after the dose application. On the other hand, when next dose is taken, plasma level is quite low.
  • EP 0673649 describes the extended release form prepared with a coat made of a polymer insoluble in water and a plastifiying agent.
  • JP61212517 describes trimetazidine matrix tablet in which hydroxypropyl methylcellulosephytalate, cellulose acetate phytalate as polymeric matrix.
  • EP 1108424 describes the extended release trimetazidine tablets prepared by wet granulation in which cellulose derivatives were used as matrix.
  • the characteristic of the patent is the controlling of extended release by a cellulose derivative polymer chosen among cellulose ethers, hydroxypropylcellulose, hydroxyethylcellulose, hydroxymethy!cellulose, methyl cellulose, hydroxypropyl methyl cellulose. Hydroxy propyl methyl cellulose was preferentially used as a cellulose derivative.
  • EP1195160 describes the extended release form, generated with trimetazidine and at least one or more hydrocolloidal material, one or more hydrophobic polymer and at least one or more other hydrophobic materials.
  • EP1448173 describes the spheres of trimetazide, extended release of which were provided by coating with polymers insoluble in water.
  • WO2009034541 describes the matrix tablets prepared by polymers insoluble or swelling in water or a mix of these two. Xanthane gum was used as polymer swelling in water.
  • Y-145 is not present in pharmacopeia (Computer Assisted Optimization and Validation of LC Analysis of Trimetazidine dihydrochloride and its Impurities, J. Chrom.ScL.Vol 46 May/June 2008).
  • This compound is chemically 4-(2,3,4-trimethoxybenzyl)- 1-piperazinecarbaldehyde hydrochloride compound. Relative retension time of this compound was found to be 0.31 in HPLC test performed in conformity with European Pharmacopeia.
  • Polyethylene oxide used in the formulation, is a water soluble resin and is also known by the trade name Polyox WSR 303. Viscosity of 1% solution is 7500-10000. It is used in 15-40%, preferably 28-32% concentration in the formulation.
  • pH buffer agent calcium phosphate dibasic dihydrate Due to pH buffer agent calcium phosphate dibasic dihydrate in the formulation, similar release was observed in all pH levels of the digestive system. It is used in 45-70%, preferably 50-54%) concentration in the formulation.
  • Formula 1-3 was prepared by wet granulation and 4-5 by direct compressing.
  • Figure 2 Dissolution profile of formulation 4 in pH:1.2. 5.4 and 6.8 environment.

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)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une forme à libération lente préparée par compression directe à l'aide d'un oxyde de polyéthylène. La formulation présente un profil de libération stable dans les limites du pH du système gastro-intestinal et une stabilité face aux impuretés.
PCT/TR2010/000173 2010-03-12 2010-09-01 Comprimés de trimétazidine à libération lente Ceased WO2011112160A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2010/01902A TR201001902A2 (tr) 2010-03-12 2010-03-12 Uzatılmış salınımlı trimetazidin tablet
TR2010/01902 2010-03-12

Publications (1)

Publication Number Publication Date
WO2011112160A1 true WO2011112160A1 (fr) 2011-09-15

Family

ID=43244791

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2010/000173 Ceased WO2011112160A1 (fr) 2010-03-12 2010-09-01 Comprimés de trimétazidine à libération lente

Country Status (2)

Country Link
TR (1) TR201001902A2 (fr)
WO (1) WO2011112160A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102885795A (zh) * 2012-10-31 2013-01-23 广州帝奇医药技术有限公司 盐酸曲美他嗪缓释片及其制备方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61212517A (ja) 1985-03-18 1986-09-20 Nippon Chemiphar Co Ltd 持続性錠剤
EP0673649A1 (fr) 1994-03-24 1995-09-27 Adir Et Compagnie Compositions pharmaceutiques permettant la libération prolongée de trimétazidine après administration par voie orale
EP1108424A1 (fr) 1999-12-17 2001-06-20 Adir Et Compagnie Comprimé matriciel permettant la libération prolongée de trimétazidine après administration par voie orale
EP1195160A1 (fr) 2000-10-05 2002-04-10 USV Ltd. Composition pharmaceutique à effet de retard contenant de la trimétazidine et procédé pour sa préparation
EP1448173A2 (fr) 2001-11-21 2004-08-25 Themis Laboratories Private Limited Procede de fabrication d'une composition pharmaceutique a liberation prolongee contenant des microbilles de trimetazidine dihydrochloride
WO2006123073A1 (fr) * 2005-05-18 2006-11-23 Les Laboratoires Servier Composition pharmaceutique solide a liberation prolongee de 1-(2,3,4-trimethoxybenzyl)piperazine, et procede de preparation.
WO2009034541A2 (fr) 2007-09-11 2009-03-19 Ranbaxy Laboratories Limited Formes galéniques à libération contrôlée à base de trimétazidine
WO2009066315A2 (fr) * 2007-08-08 2009-05-28 Usv Limited Compositions à libération prolongée de trimétazidine et procédé de préparation

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61212517A (ja) 1985-03-18 1986-09-20 Nippon Chemiphar Co Ltd 持続性錠剤
EP0673649A1 (fr) 1994-03-24 1995-09-27 Adir Et Compagnie Compositions pharmaceutiques permettant la libération prolongée de trimétazidine après administration par voie orale
EP1108424A1 (fr) 1999-12-17 2001-06-20 Adir Et Compagnie Comprimé matriciel permettant la libération prolongée de trimétazidine après administration par voie orale
EP1195160A1 (fr) 2000-10-05 2002-04-10 USV Ltd. Composition pharmaceutique à effet de retard contenant de la trimétazidine et procédé pour sa préparation
EP1448173A2 (fr) 2001-11-21 2004-08-25 Themis Laboratories Private Limited Procede de fabrication d'une composition pharmaceutique a liberation prolongee contenant des microbilles de trimetazidine dihydrochloride
WO2006123073A1 (fr) * 2005-05-18 2006-11-23 Les Laboratoires Servier Composition pharmaceutique solide a liberation prolongee de 1-(2,3,4-trimethoxybenzyl)piperazine, et procede de preparation.
WO2009066315A2 (fr) * 2007-08-08 2009-05-28 Usv Limited Compositions à libération prolongée de trimétazidine et procédé de préparation
WO2009034541A2 (fr) 2007-09-11 2009-03-19 Ranbaxy Laboratories Limited Formes galéniques à libération contrôlée à base de trimétazidine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Computer Assisted Optimization and Validation of LC Analysis of Trimetazidine dihydrochloride and its Impurities", J. CHROM.SCI., vol. 46, May 2008 (2008-05-01)
MEDENICA MIRJANA B ET AL: "Computer-assisted optimization and validation of LC analysis of trimetazidine dihydrochloride and its impurities", JOURNAL OF CHROMATOGRAPHIC SCIENCE, PRESTON PUBLICATIONS, NILES, IL, US, vol. 46, no. 5, 1 May 2008 (2008-05-01), pages 430 - 435, XP009142314, ISSN: 0021-9665 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102885795A (zh) * 2012-10-31 2013-01-23 广州帝奇医药技术有限公司 盐酸曲美他嗪缓释片及其制备方法

Also Published As

Publication number Publication date
TR201001902A2 (tr) 2011-04-21

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