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RU2013110058A - PHARMACEUTICAL GRANULATE CONTAINING IMATINIB MESILATE - Google Patents

PHARMACEUTICAL GRANULATE CONTAINING IMATINIB MESILATE Download PDF

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Publication number
RU2013110058A
RU2013110058A RU2013110058/15A RU2013110058A RU2013110058A RU 2013110058 A RU2013110058 A RU 2013110058A RU 2013110058/15 A RU2013110058/15 A RU 2013110058/15A RU 2013110058 A RU2013110058 A RU 2013110058A RU 2013110058 A RU2013110058 A RU 2013110058A
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RU
Russia
Prior art keywords
imatinib mesylate
granulate
composition
granulator
liquid
Prior art date
Application number
RU2013110058/15A
Other languages
Russian (ru)
Inventor
ден Хевел Денни Йохан Марейн Ван
Original Assignee
Синтон Б.В.
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 Синтон Б.В. filed Critical Синтон Б.В.
Publication of RU2013110058A publication Critical patent/RU2013110058A/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682Processes
    • A61K9/1688Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2095Tabletting 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

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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

1. Гранулят, содержащий 95-99% иматиниба мезилата и 1-5% летучей жидкости.2. Гранулят по п.1, где иматиниба мезилат представляет собой кристаллический иматиниба мезилат, предпочтительно кристаллический иматиниба мезилат формы α, получаемый путем осаждения кристаллического иматиниба мезилата формы α из раствора иматиниба мезилата в растворителе, отличном от метанола, таком как этанол, и без добавления затравочного кристалла β-кристаллической формы иматиниба мезилата.3. Гранулят по п.1 или 2, где летучая жидкость представляет собой воду, этанол, изопропанол и их смеси.4. Гранулят по п.1, состоящий из гранул, имеющих средний размер 250-800 мкм.5. Способ получения гранулята иматиниба мезилата, который включает смачивание иматиниба мезилата жидкостью для грануляции и грануляцию смеси в грануляторе с последующим высушиванием, и необязательно просеивание и/или измельчение полученной совокупности гранул.6. Способ по п.5, где жидкостью для грануляции является вода, этанол и/или изопропанол.7. Способ по п.5 или 6, где количество жидкости для грануляции составляет 5-50 масс.% относительно массы иматиниба мезилата.8. Способ по п.5, где гранулятор представляет собой гранулятор с высоким сдвиговым усилием или гранулятор с псевдоожиженным слоем.9. Фармацевтическая композиция для перорального введения иматиниба мезилата, содержащая гранулят иматиниба мезилата по пп.1-4 и/или изготовленная по пп.5-8, и необязательно по меньшей мере один фармацевтически приемлемый эксципиент.10. Композиция по п.9 в форме таблетки.11. Композиция по п.9 или 10, содержащая по меньшей мере 50 масс.%, более предпочтительно по меньшей мере 60 масс.% гранулята.12. Композиция по п.91. Granulate containing 95-99% imatinib mesylate and 1-5% volatile liquid. 2. The granulate according to claim 1, wherein the imatinib mesylate is crystalline imatinib mesylate, preferably crystalline imatinib mesylate form α, obtained by precipitating crystalline imatinib mesylate form α from a solution of imatinib mesylate in a solvent other than methanol, such as ethanol, and without the addition of a seed crystal. β-crystalline form of imatinib mesylate. 3. The granulate according to claim 1 or 2, wherein the volatile liquid is water, ethanol, isopropanol and mixtures thereof. The granulate according to claim 1, consisting of granules having an average size of 250-800 microns. A method for producing imatinib mesylate granulate, which comprises wetting imatinib mesylate with granulation liquid and granulating the mixture in a granulator, followed by drying, and optionally sieving and / or grinding the resulting granule set. 6. The method of claim 5, wherein the granulation liquid is water, ethanol and / or isopropanol. The method according to claim 5 or 6, where the amount of liquid for granulation is 5-50 wt.% Relative to the weight of imatinib mesylate. The method of claim 5, wherein the granulator is a high shear granulator or a fluidized bed granulator. A pharmaceutical composition for oral administration of imatinib mesylate containing imatinib mesylate granules according to claims 1-4 and / or manufactured according to claims 5-8, and optionally at least one pharmaceutically acceptable excipient. 10. The composition of claim 9 in tablet form. A composition according to claim 9 or 10, containing at least 50 wt.%, More preferably at least 60 wt.% Of the granulate. The composition according to claim 9

Claims (18)

1. Гранулят, содержащий 95-99% иматиниба мезилата и 1-5% летучей жидкости.1. A granulate containing 95-99% imatinib mesylate and 1-5% volatile liquid. 2. Гранулят по п.1, где иматиниба мезилат представляет собой кристаллический иматиниба мезилат, предпочтительно кристаллический иматиниба мезилат формы α, получаемый путем осаждения кристаллического иматиниба мезилата формы α из раствора иматиниба мезилата в растворителе, отличном от метанола, таком как этанол, и без добавления затравочного кристалла β-кристаллической формы иматиниба мезилата.2. The granulate according to claim 1, wherein the imatinib mesylate is crystalline imatinib mesylate, preferably crystalline imatinib mesylate form α, obtained by precipitating crystalline imatinib mesylate form α from a solution of imatinib mesylate in a solvent other than methanol, such as ethanol, and without addition a seed crystal of a β-crystalline form of imatinib mesylate. 3. Гранулят по п.1 или 2, где летучая жидкость представляет собой воду, этанол, изопропанол и их смеси.3. The granulate according to claim 1 or 2, where the volatile liquid is water, ethanol, isopropanol and mixtures thereof. 4. Гранулят по п.1, состоящий из гранул, имеющих средний размер 250-800 мкм.4. The granulate according to claim 1, consisting of granules having an average size of 250-800 microns. 5. Способ получения гранулята иматиниба мезилата, который включает смачивание иматиниба мезилата жидкостью для грануляции и грануляцию смеси в грануляторе с последующим высушиванием, и необязательно просеивание и/или измельчение полученной совокупности гранул.5. A method for producing imatinib mesylate granulate, which comprises wetting imatinib mesylate with granulation liquid and granulating the mixture in a granulator, followed by drying, and optionally sieving and / or grinding the resulting granule set. 6. Способ по п.5, где жидкостью для грануляции является вода, этанол и/или изопропанол.6. The method according to claim 5, where the liquid for granulation is water, ethanol and / or isopropanol. 7. Способ по п.5 или 6, где количество жидкости для грануляции составляет 5-50 масс.% относительно массы иматиниба мезилата.7. The method according to claim 5 or 6, where the amount of liquid for granulation is 5-50 wt.% Relative to the weight of imatinib mesylate. 8. Способ по п.5, где гранулятор представляет собой гранулятор с высоким сдвиговым усилием или гранулятор с псевдоожиженным слоем.8. The method according to claim 5, where the granulator is a high shear granulator or a fluidized bed granulator. 9. Фармацевтическая композиция для перорального введения иматиниба мезилата, содержащая гранулят иматиниба мезилата по пп.1-4 и/или изготовленная по пп.5-8, и необязательно по меньшей мере один фармацевтически приемлемый эксципиент.9. A pharmaceutical composition for oral administration of imatinib mesylate containing granules of imatinib mesylate according to claims 1-4 and / or made according to claims 5-8, and optionally at least one pharmaceutically acceptable excipient. 10. Композиция по п.9 в форме таблетки.10. The composition according to claim 9 in the form of a tablet. 11. Композиция по п.9 или 10, содержащая по меньшей мере 50 масс.%, более предпочтительно по меньшей мере 60 масс.% гранулята.11. The composition according to claim 9 or 10, containing at least 50 wt.%, More preferably at least 60 wt.% Of the granulate. 12. Композиция по п.9, содержащая от 50 мг до 800 мг, в частности 100 мг и 400 мг иматиниба в расчете на свободное основание.12. The composition according to claim 9, containing from 50 mg to 800 mg, in particular 100 mg and 400 mg of imatinib, based on the free base. 13. Способ получения фармацевтической композиции для перорального введения иматиниба мезилата по пп.9-12, включающий стадию сухого смешения гранулята иматиниба мезилата с эксципиентами.13. A method of obtaining a pharmaceutical composition for oral administration of imatinib mesylate according to claims 9-12, comprising the step of dry mixing the imatinib mesylate granulate with excipients. 14. Способ по п.13, дополнительно включающий стадию прессования композиции в таблетки.14. The method of claim 13, further comprising the step of compressing the composition into tablets. 15. Гранулят по п.1 для применения в медицине, такого как лечение различных типов злокачественных заболеваний.15. The granulate according to claim 1 for use in medicine, such as the treatment of various types of malignant diseases. 16. Гранулят изготовленный по п.5, для применения в медицине, такого как лечение различных типов злокачественных заболеваний.16. The granulate made according to claim 5, for use in medicine, such as the treatment of various types of malignant diseases. 17. Композиция по п.9 для применения в медицине, такого как лечение различных типов злокачественных заболеваний.17. The composition according to claim 9 for use in medicine, such as the treatment of various types of malignant diseases. 18. Композиция изготовленная по п.13 для применения в медицине, такого как лечение различных типов злокачественных заболеваний. 18. The composition made according to item 13 for use in medicine, such as the treatment of various types of malignant diseases.
RU2013110058/15A 2010-08-11 2010-08-11 PHARMACEUTICAL GRANULATE CONTAINING IMATINIB MESILATE RU2013110058A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2010/005214 WO2012019633A1 (en) 2010-08-11 2010-08-11 Pharmaceutical granulate comprising imatinib mesylate

Publications (1)

Publication Number Publication Date
RU2013110058A true RU2013110058A (en) 2014-09-20

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RU2013110058/15A RU2013110058A (en) 2010-08-11 2010-08-11 PHARMACEUTICAL GRANULATE CONTAINING IMATINIB MESILATE

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EP (1) EP2603288A1 (en)
MX (1) MX2013001653A (en)
RU (1) RU2013110058A (en)
WO (1) WO2012019633A1 (en)
ZA (1) ZA201300872B (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9750700B2 (en) * 2011-06-22 2017-09-05 Natco Pharma Limited Imatinib mesylate oral pharmaceutical composition and process for preparation thereof
IN2014DN07898A (en) * 2012-02-21 2015-04-24 Ranbaxy Lab Ltd
EP2749271A1 (en) * 2012-12-31 2014-07-02 Deva Holding Anonim Sirketi Optimized manufacturing method and pharmaceutical formulation of imatinib
EP2803353B1 (en) 2013-05-14 2018-05-23 Hetero Research Foundation Compositions of Imatinib
AU2014288866B2 (en) * 2013-07-09 2017-07-13 Shilpa Medicare Limited Oral pharmaceutical compositions comprising Imatinib mesylate
EP3257499A1 (en) 2016-06-17 2017-12-20 Vipharm S.A. Process for preparation of imatinib methanesulfonate capsules

Family Cites Families (9)

* Cited by examiner, † Cited by third party
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US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
TW225528B (en) 1992-04-03 1994-06-21 Ciba Geigy Ag
CO4940418A1 (en) 1997-07-18 2000-07-24 Novartis Ag MODIFICATION OF A CRYSTAL OF A DERIVATIVE OF N-PHENYL-2-PIRIMIDINAMINE, PROCESSES FOR ITS MANUFACTURE AND USE
GB0209265D0 (en) * 2002-04-23 2002-06-05 Novartis Ag Organic compounds
WO2006040779A2 (en) 2004-10-11 2006-04-20 Natco Pharma Limited Controlled release gastric floating matrix formulation containing imatinib
MY148074A (en) 2005-05-10 2013-02-28 Novartis Ag Pharmaceutical compositions comprising imatinib and a release retardant
ES2334933T3 (en) 2005-08-15 2010-03-17 Siegfried Generics International Ag COVERED OR GRANULATED TABLET CONTAINING A PYRIDYL PIRIMIDINE.
PL390611A1 (en) * 2010-03-04 2011-09-12 Tomasz Koźluk Process for the preparation of polymorphic alpha form and new polymorphic form of imatinib mesylate
EP2552447A4 (en) * 2010-03-29 2013-09-11 Hetero Research Foundation Stable pharmaceutical composition of imatinib

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WO2012019633A1 (en) 2012-02-16
MX2013001653A (en) 2013-05-22
EP2603288A1 (en) 2013-06-19
ZA201300872B (en) 2014-04-30

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