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WO2012019633A1 - Granulat pharmaceutique comprenant de l'imatinib mésylate - Google Patents

Granulat pharmaceutique comprenant de l'imatinib mésylate Download PDF

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Publication number
WO2012019633A1
WO2012019633A1 PCT/EP2010/005214 EP2010005214W WO2012019633A1 WO 2012019633 A1 WO2012019633 A1 WO 2012019633A1 EP 2010005214 W EP2010005214 W EP 2010005214W WO 2012019633 A1 WO2012019633 A1 WO 2012019633A1
Authority
WO
WIPO (PCT)
Prior art keywords
imatinib mesylate
granulate
imatinib
composition
mesylate
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/EP2010/005214
Other languages
English (en)
Inventor
Dennie Johan Marijn Van Den Heuvel
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.)
Synthon BV
Original Assignee
Synthon BV
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 Synthon BV filed Critical Synthon BV
Priority to PCT/EP2010/005214 priority Critical patent/WO2012019633A1/fr
Priority to RU2013110058/15A priority patent/RU2013110058A/ru
Priority to MX2013001653A priority patent/MX2013001653A/es
Priority to EP10747433.0A priority patent/EP2603288A1/fr
Publication of WO2012019633A1 publication Critical patent/WO2012019633A1/fr
Priority to ZA2013/00872A priority patent/ZA201300872B/en
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
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
    • 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
    • A61K9/2095—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • ABL protein tyrosine kinase is a pharmaceutically active compound acting as a selective inhibitor of the ABL protein tyrosine kinase.
  • a (mono)mesylate salt it has been used in a medicament for the treatment of various types of cancer diseases, and is available, e.g. under the brand name GLIVEC®, as 100 mg and 400 mg tablets for oral administration.
  • Imatinib and its salts have been disclosed in EP B 564409 (US 5521 184). Specifically, imatinib mesylate and its crystalline polymorphic Forms a and ⁇ are disclosed in WO 99/03854.
  • EP 564409 and WO 99/03854 disclose generically many possible formulations, which are prepared in a manner known per se, for example by means of conventional mixing, granulating, dissolving or lyophilizing processes, and comprise approximately from 1% to 100%, especially from approximately 1% to approximately 20%, active ingredient.
  • direct compression, gelatinizing and mixing techniques are disclosed.
  • WO 2006/040779 discloses wet granulation of imatinib mesylate (10% to 80%) with gelling agents, gas generating components and a binding solution to form a granulate.
  • WO 2006/121941 discloses a melt granulation process which comprises the steps of (a) forming a mixture of imatinib mesylate with at least one release retardant, e.g., a release retarding polymer, a plasticizer or a release modifier; (b) granulating the mixture using an extruder and (c) cooling the granules.
  • a release retardant e.g., a release retarding polymer, a plasticizer or a release modifier
  • US 2007/0036850 discloses a dry granulation (by compaction) process for the preparation of imatinib Form a or ⁇ granules prior to the tabletting process.
  • the imatinib granule cores contain between 25 and 80% of imatinib together with filler-binder additives , e.g. with microcrystalline cellulose and crospovidone.
  • Granulation processes of the prior art have been developed, in particular, because of bad tabletting properties of imatinib mesylate itself, in particular its crystalline Form a. While many such procedures are known in the art, an improvement in this field, in particular by finding a simple and easy scalable process of improving tabletting properties of imatinib mesylate, is still desirable.
  • the present invention relates to pharmaceutical granules comprising imatinib mesylate.
  • the granules are prepared by wet granulation process without the use of additional excipients, such as binders, except for the granulation liquid.
  • the granules are useful in making pharmaceutical compositions, particularly tablets, preferably by direct compression with suitable excipients.
  • the present invention provides a granulate containing 95-99 % of imatinib mesylate, in particular crystalline imatinib mesylate and in more particular the polymorphic Form a of imatinib mesylate , and 1-5% of a volatile liquid, preferably water, ethanol, isopropanol and mixtures thereof.
  • the population of granules has an average size of between 250-800 ⁇ , as determined by sieve analysis.
  • the invention provides a process for making a granulate comprising imatinib mesylate, which process comprises wetting imatinib mesylate with a granulation liquid, which is preferably water, ethanol and/or isopropanol and most preferably in an amount of 5 - 50 weight %, in respect to the mass of imatinib mesylate, and granulating the mixture in a suitable granulator, e.g. high shear or fluid bed granulator, followed by drying, and optionally sieving and/or milling of the produced population of granules.
  • a suitable granulator e.g. high shear or fluid bed granulator
  • the invention provides a pharmaceutical composition for oral administration of imatinib mesylate, comprising the imatinib mesylate granulate of the preceded aspects, and ,optionally, at least one pharmaceutically acceptable excipient. It also provides a pharmaceutical tablet of imatinib mesylate comprising the above pharmaceutical composition in a compressed form.
  • the invention provides a process for making pharmaceutical composition and/or pharmaceutical tablet comprising imatinib mesylate, wherein the process comprises steps of dry admixing the imatinib mesylate granulate of the present invention with excipients to provide a composition, and optionally, compressing the composition into tablets comprising the therapeutical dose of imatinib.
  • the last aspect deals with the use of the pharmaceutical imatinib mesylate granulate of the present invention and/or a composition comprising it for making a medicament.
  • Imatinib mesylate is a generic term for N- ⁇ 5- [4- (4- methyl-piperazino- methyl)-benzoylamido]-2-methylphenyl ⁇ -4- (3-pyridyl)-2-pyrimidine-amine (mono)methane sulfonate.
  • the crystalline "form a" of imatinib mesylate and the crystalline "form ⁇ " of imatinib mesylate are polymorphic forms as prepared and characterized by methods disclosed in WO 99/03854.
  • the form a is obtainable according to WO 99/03854 for example by precipitating out the crystalline imatinib mesylate Form a from a solution comprising imatinib mesylate, in a solvent other than methanol, for instance in ethanol, and without adding a seed crystal of the ⁇ -crystal form of imatinib mesylate.
  • a typical process is shown in the Example 1 of WO 99/03854. As no single decisive parameter has been used therein for sufficient
  • Imatinib mesylate (and particularly the form a) has, in general, bad tabletting properties for direct compression with excipients. Therefore any prior art process of making solid
  • compositions comprising imatinib mesylate and useful for making compressed dosage forms, such as tablets, comprises the step of granulation of imatinib with filler-binders excipients to yield a "composite" granulate, i.e. a granulate comprising imatinib and at least one granulate-forming excipient.
  • the "wet granulation” as used herein is a process, which itself is well known in the art and comprises, within many technological variants, moistening a solid component or a mixture of solid components with a liquid, and vigorous mixing of the composition, whereby the wet particles of solids adhere together by cohesive forces to form larger, sometimes essentially spherical, agglomerates (a granulate).
  • the excess of the granulation liquid may be removed from the raw granulate by drying and the suitable size range of particles is obtained by sieving and/or milling the population of granules.
  • imatinib mesylate can be wet granulated without using any granulate-forming excipient, such as a filler and/or binder , to form a free flowing solid granulate material comprising ,based on a solvent-free basis, only imatinib (small amounts of used granulation liquid may be present).
  • a granulation liquid which is preferably water and/or an alcohol, e.g. ethanol or isopropanol, and processing the mixture in a suitable granulator results in a stable free flowing granulate form of imatinib mesylate with suitable characteristics for further processing.
  • Imatinib mesylate is thereby obtained in a free-flowing form, which is well compatible with pharmaceutical excipients and is suitable for direct tabletting. Also the tap density of the compound is enhanced, thus minimizing the danger of segregation during dry mixing with excipients.
  • the granulate is compatible with broader spectrum of useful excipients, as it now can be mixed with the excipients, which were currently not suitable in the techniques used so far.
  • the present invention thus provides a granulate form of imatinib mesylate, characterized in that smaller particles (crystals) of imatinib mesylate are agglomerated into granules.
  • the granulate is free from granulation-aiding excipients such as binders or fillers, consisting only from imatinib mesylate (typically 95-99 weight% ) and rests of volatile liquid (typically 1 -5 weight %) from the granulation process, which liquid is preferably water, ethanol, isopropanol and mixtures thereof.
  • the amount of the residual volatiles may be determined by standard analytical techniques, e.g. by a determination of a loss on drying according to a process of European Pharmacopoeia.
  • the advantageous granulate population is generally comprised of granules having an average size of between 250-800 ⁇ .
  • the particle size of the population of granules may be adjusted by optional milling and/or sieving of the raw granules. Typically, two sieves of different mesh size are applied, and a population of granules passing the higher mesh and not passing the lower mesh size is used for further processing.
  • Sieve analysis i.e. measuring and calculating the relative proportions of particles that pass sieves of different mesh sizes, may be also used for determining the average particle size of the population of granules.
  • the granulate may be made from any solid form of imatinib mesylate.
  • the "solid form” may comprise crystalline or amorphous form.
  • the "crystalline form” may comprise Form a or Form ⁇ , as defined above.
  • the granulate comprises the Form a of crystalline imatinib mesylate. It is important to note that, quite surprisingly, it was found that making a granulate from the Form a under conditions disclosed below does not result in any polymorphic transformation of imatinib, albeit the Form a has been reported metastable at ambient conditions.
  • the present invention allows to formulate the metastable Form a of imatinib mesylate in pharmaceutical compositions, with a minimal risk that such form shall be transformed in Form ⁇ . Analytical processes allow to determine the relative amounts of both forms.
  • the granulate of the present invention is produced by a wet granulation process.
  • the process typically comprises adding solid imatinib mesylate to a granulator and mixing there with a granulation liquid to form a population of granules.
  • a high shear or a fluid bed granulator may be used.
  • the granulation liquid is advantageously water, an alcohol such as ethanol or isopropanol, and mixtures thereof.
  • the suitable amount of the granulation liquid is about 5 - 50 weight %, relatively to the amount of imatinib mesylate.
  • the amount of water may be from 5 to 20%, the amount of ethanol from 20 to 40%, that of isopropanol from 30 to 50%.
  • a drying step is generally performed to remove essentially all amount of the granulation liquid.
  • the drying step may include using a vacuum, microwave radiation, heating air, heating double-jacket, and/or gas flow (N 2 or air).
  • the advantageous limit for the content of residual volatiles is from 1 to 5 %.
  • the resulting dried granulate may be milled and/or sieved to obtain a free flowing granulate population of the desired particle size.
  • the granules produced according to the present invention are, in essence, well cohesive so that they may be subjected to a gentle milling, which is useful in order to minimize the percentage of higher agglomerates.
  • the imatinib mesylate granulate of the present invention may be used in making medicaments, particularly medicaments for oral administration of imatinib to a patient in need thereof.
  • the granulate may be formulated advantageously with at least one suitable excipient, into pharmaceutical compositions and further processed into various pharmaceutical dosage forms comprising the pharmaceutical dose of imatinib.
  • the final dosage form e.g. a capsule or a sachet
  • the imatinib mesylate granulate may also comprise solely the imatinib mesylate granulate, thus it may contain 100 % of the imatinib mesylate ( when excluding the residual volatiles) , which was not possible in any prior art formulation.
  • the imatinib mesylate granulate of the present invention may be mixed in a suitable mixer, e.g., a free fall blender, with auxiliary excipients, such as filler(s), binder (s) disintegrant(s), lubricant(s), glidant(s), to provide an homogeneous mixture of desired properties and concentration of the active substance.
  • auxiliary excipients such as filler(s), binder (s) disintegrant(s), lubricant(s), glidant(s), to provide an homogeneous mixture of desired properties and concentration of the active substance.
  • auxiliary excipients such as filler(s), binder (s) disintegrant(s), lubricant(s), glidant(s), to provide an homogeneous mixture of desired properties and concentration of the active substance.
  • all components are admixed in a dry state.
  • the filler binder include microcrystalline cellulose and cellulose derivatives, polyvinylpyrrolidon
  • the lubricant is magnesium stearate.
  • An example of the glidant is silicon dioxide.
  • the amounts and type of the auxiliary excipients depend on the desired physical properties of the final composition and desired concentration of imatinib mesylate.
  • the granulate-comprising pharmaceutical composition of the present invention may be used in making solid dosage forms for oral administration, typically capsules or tablets. In the latter case, the pharmaceutical composition is compressed into tablets in a suitable tablet press. The tablets may be round, oval, biconvex or of other suitable shape. If desirable, the tablets may be coated, for instance by a water soluble film-coat, to improve the handling properties. Examples of coating material are an HPMC based coating, a polyvinylalcohol based coating or a polyethylene glycol-polyvinylalcohol based coating. Relative amount of the coating is typically from 2 to 6 %.
  • the granulate is suitable for making a composition for direct filling into capsules or sachets, optionally even without adding any auxiliary excipient.
  • the relative amount of the granulated form of imatinib mesylate in the pharmaceutical composition is at least 50 weight %, more preferably at least 60 weight %.
  • compositions comprising 100% of imatinib mesylate are included.
  • the absolute amount of imatinib is preferably within the range from 50mg to 800mg, especially of 1 OOmg, and of 400 mg, calculated as free base.
  • Imatinib mesylate Form a granulate 63.7 1 19.5 478
  • Weight core 100 187.5 750 Process ;

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

Abstract

La présente invention concerne un granulat contenant entre 95 et 99 % d'imatinib mésylate et entre 1 et 5 % d'un liquide volatil. L'invention porte en outre sur un procédé de fabrication d'un granulat d'imatinib mésylate. Ledit procédé comprend le mouillage d'imatinib mésylate avec un liquide de granulation, et la granulation du mélange dans un granulateur, suivie du séchage, et éventuellement du tamisage et/ou du broyage de la population produite de granules, en vue d'obtenir une composition pharmaceutique pour administration orale destinée à être utilisée en médecine.
PCT/EP2010/005214 2010-08-11 2010-08-11 Granulat pharmaceutique comprenant de l'imatinib mésylate Ceased WO2012019633A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
PCT/EP2010/005214 WO2012019633A1 (fr) 2010-08-11 2010-08-11 Granulat pharmaceutique comprenant de l'imatinib mésylate
RU2013110058/15A RU2013110058A (ru) 2010-08-11 2010-08-11 Фармацевтический гранулят, содержащий иматиниба мезилат
MX2013001653A MX2013001653A (es) 2010-08-11 2010-08-11 Granulado farmaceutico que comprende mesilato de imatinib
EP10747433.0A EP2603288A1 (fr) 2010-08-11 2010-08-11 Granulat pharmaceutique comprenant de l'imatinib mésylate
ZA2013/00872A ZA201300872B (en) 2010-08-11 2013-02-01 Pharmaceutical granulate comprising imatinib mesylate

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2010/005214 WO2012019633A1 (fr) 2010-08-11 2010-08-11 Granulat pharmaceutique comprenant de l'imatinib mésylate

Publications (1)

Publication Number Publication Date
WO2012019633A1 true WO2012019633A1 (fr) 2012-02-16

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ID=44065563

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2010/005214 Ceased WO2012019633A1 (fr) 2010-08-11 2010-08-11 Granulat pharmaceutique comprenant de l'imatinib mésylate

Country Status (5)

Country Link
EP (1) EP2603288A1 (fr)
MX (1) MX2013001653A (fr)
RU (1) RU2013110058A (fr)
WO (1) WO2012019633A1 (fr)
ZA (1) ZA201300872B (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120329810A1 (en) * 2011-06-22 2012-12-27 Natco Pharma Limited Imatinib mesylate oral pharmaceutical composition and process for preparation thereof
WO2013124774A1 (fr) * 2012-02-21 2013-08-29 Ranbaxy Laboratories Limited Formes posologiques stables de mésylate d'imatinib
EP2749271A1 (fr) * 2012-12-31 2014-07-02 Deva Holding Anonim Sirketi Procédé optimisée de fabrication et formulation pharmaceutique de l'imatinib
EP2803353A1 (fr) 2013-05-14 2014-11-19 Hetero Research Foundation Compositions d'imatinib
WO2015004556A1 (fr) * 2013-07-09 2015-01-15 Shilpa Medicare Limited Compositions pharmaceutiques orales comprenant du mésylate d'imatinib
EP3257499A1 (fr) 2016-06-17 2017-12-20 Vipharm S.A. Procédé pour la préparation de capsules de méthanesulfonate d'imatinib

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
WO1999003854A1 (fr) 1997-07-18 1999-01-28 Novartis Ag Modification de la forme cristalline d'un derive n-phenyl-2-pyrimidineamine, procede de preparation et d'utilisation de ce dernier
EP0564409B1 (fr) 1992-04-03 2000-01-19 Novartis AG Dérivés de pyrimidine et procédé pour leur préparation
WO2003090720A1 (fr) * 2002-04-23 2003-11-06 Novartis Ag Comprime a forte charge en substance medicamenteuse
WO2006040779A2 (fr) 2004-10-11 2006-04-20 Natco Pharma Limited Formule à matrice flottante gastrique à libération contrôlée contenant la substance imatinib
WO2006121941A2 (fr) 2005-05-10 2006-11-16 Novartis Ag Compositions pharmaceutiques comprenant l'imatinibe et un retardateur de liberation
US20070036850A1 (en) 2005-08-15 2007-02-15 Siegfried Generics International Ag Film-coated tablet or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound
WO2011108953A1 (fr) * 2010-03-04 2011-09-09 Tomasz Kozluk Procédé pour la préparation de forme polymorphe α et nouvelle forme polymorphe d'imatinib mésylate isolée dans ce procédé
WO2011121593A1 (fr) * 2010-03-29 2011-10-06 Hetero Research Foundation Composition pharmaceutique stable d'imatinib

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
EP0564409B1 (fr) 1992-04-03 2000-01-19 Novartis AG Dérivés de pyrimidine et procédé pour leur préparation
WO1999003854A1 (fr) 1997-07-18 1999-01-28 Novartis Ag Modification de la forme cristalline d'un derive n-phenyl-2-pyrimidineamine, procede de preparation et d'utilisation de ce dernier
WO2003090720A1 (fr) * 2002-04-23 2003-11-06 Novartis Ag Comprime a forte charge en substance medicamenteuse
EP1501485A1 (fr) 2002-04-23 2005-02-02 Novartis AG Comprime a forte charge en substance medicamenteuse
WO2006040779A2 (fr) 2004-10-11 2006-04-20 Natco Pharma Limited Formule à matrice flottante gastrique à libération contrôlée contenant la substance imatinib
WO2006121941A2 (fr) 2005-05-10 2006-11-16 Novartis Ag Compositions pharmaceutiques comprenant l'imatinibe et un retardateur de liberation
US20070036850A1 (en) 2005-08-15 2007-02-15 Siegfried Generics International Ag Film-coated tablet or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound
WO2011108953A1 (fr) * 2010-03-04 2011-09-09 Tomasz Kozluk Procédé pour la préparation de forme polymorphe α et nouvelle forme polymorphe d'imatinib mésylate isolée dans ce procédé
WO2011121593A1 (fr) * 2010-03-29 2011-10-06 Hetero Research Foundation Composition pharmaceutique stable d'imatinib

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Granulate ED - Schöffling; Ursula", 1 January 2009, ARZNEIFORMENLEHRE: EIN LEHRBUCH DER GALENIK FÜR THEORIE UND PRAXIS, DT. APOTHEKER-VERLAG, DE, PAGE(S) 173 - 185, ISBN: 978-3-7692-4093-1, XP009153545 *
"Stable Tablet Formulation containing more than 80% of Imatinib mesylate", IP.COM JOURNAL, IP.COM INC., WEST HENRIETTA, NY, US, 19 February 2008 (2008-02-19), XP013123894, ISSN: 1533-0001 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120329810A1 (en) * 2011-06-22 2012-12-27 Natco Pharma Limited Imatinib mesylate oral pharmaceutical composition and process for preparation thereof
WO2012176014A1 (fr) * 2011-06-22 2012-12-27 Natco Pharma Limited Composition pharmaceutique orale de mésylate d'imatinib et son procédé de préparation
US9750700B2 (en) * 2011-06-22 2017-09-05 Natco Pharma Limited Imatinib mesylate oral pharmaceutical composition and process for preparation thereof
WO2013124774A1 (fr) * 2012-02-21 2013-08-29 Ranbaxy Laboratories Limited Formes posologiques stables de mésylate d'imatinib
EP2749271A1 (fr) * 2012-12-31 2014-07-02 Deva Holding Anonim Sirketi Procédé optimisée de fabrication et formulation pharmaceutique de l'imatinib
EP2803353A1 (fr) 2013-05-14 2014-11-19 Hetero Research Foundation Compositions d'imatinib
WO2015004556A1 (fr) * 2013-07-09 2015-01-15 Shilpa Medicare Limited Compositions pharmaceutiques orales comprenant du mésylate d'imatinib
AU2014288866B2 (en) * 2013-07-09 2017-07-13 Shilpa Medicare Limited Oral pharmaceutical compositions comprising Imatinib mesylate
EP3257499A1 (fr) 2016-06-17 2017-12-20 Vipharm S.A. Procédé pour la préparation de capsules de méthanesulfonate d'imatinib

Also Published As

Publication number Publication date
RU2013110058A (ru) 2014-09-20
MX2013001653A (es) 2013-05-22
EP2603288A1 (fr) 2013-06-19
ZA201300872B (en) 2014-04-30

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