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RU2013119811A - METHOD FOR REMOVING RESIDUAL ORGANIC SOLVENT FROM MICROPARTICLES - Google Patents

METHOD FOR REMOVING RESIDUAL ORGANIC SOLVENT FROM MICROPARTICLES Download PDF

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Publication number
RU2013119811A
RU2013119811A RU2013119811/05A RU2013119811A RU2013119811A RU 2013119811 A RU2013119811 A RU 2013119811A RU 2013119811/05 A RU2013119811/05 A RU 2013119811/05A RU 2013119811 A RU2013119811 A RU 2013119811A RU 2013119811 A RU2013119811 A RU 2013119811A
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RU
Russia
Prior art keywords
microparticles
organic solvent
residual organic
surfactant
combination
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Application number
RU2013119811/05A
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Russian (ru)
Inventor
Адриан Т. РАЙХЕ
Бренда Х. ПЕРКИНС
Original Assignee
Эвоник Корпорейшн
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Publication of RU2013119811A publication Critical patent/RU2013119811A/en

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    • 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
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1641Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647Polyesters, e.g. poly(lactide-co-glycolide)
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Biological Depolymerization Polymers (AREA)
  • Processes Of Treating Macromolecular Substances (AREA)

Abstract

1. Способ уменьшения содержания остаточного органического растворителя в микрочастицах, включающий:(a) объединение микрочастиц с раствором поверхностно-активного вещества в неполярном алкане для обеспечения дисперсии;(b) смешивание дисперсии;(c) сбор микрочастиц;(d) промывание микрочастиц; и(e) сушку микрочастиц;где перед стадией (а) микрочастицы содержат по меньшей мере 2% остаточного органического растворителя, содержащего галогенированный растворитель, этилацетат или их смесь.2. Способ по п.1, в котором остаточный органический растворитель содержит С-Сгалогенированный алкан.3. Способ по п.2, в котором остаточный органический растворитель содержит С-Схлорированный алкан.4. Способ по п.3, в котором остаточный органический растворитель содержит метиленхлорид, хлороформ, тетрахлорид углерода, этилендихлорид, этиленхлорид, 2,2,2-трихлорэтан или их смесь.5. Способ по п.1, в котором остаточный органический растворитель содержит этилацетат.6. Способ по п.1, в котором поверхностно-активное вещество содержит сорбитола моностеарат, сорбитана моноолеат, полиоксиэтилен сорбитана моноолеат или их комбинацию.7. Способ по п.1, в котором микрочастицы промывают свободным от поверхностно-активного вещества неполярным алканом, водой или их комбинацией.8. Способ по п.7, в котором микрочастицы промывают свободным от поверхностно-активного вещества гептаном, водой или их комбинацией.9. Способ по п.1, в котором микрочастицы собирают посредством ситового сепарирования.10. Способ по п.1, в котором микрочастицы содержат поли(лактид), поли(гликолид), поли(лактид-со-гликолид) или их сополимер, комбинацию или смесь.11. Способ по любому из пп.1-10, в кото�1. A method of reducing the residual organic solvent in the microparticles, comprising: (a) combining the microparticles with a solution of a surfactant in a non-polar alkane to provide dispersion; (b) mixing the dispersion; (c) collecting microparticles; (d) washing the microparticles; and (e) drying the microparticles; where, before step (a), the microparticles contain at least 2% residual organic solvent containing a halogenated solvent, ethyl acetate, or a mixture thereof. The method according to claim 1, wherein the residual organic solvent contains a C-halogenated alkane. The method according to claim 2, wherein the residual organic solvent contains C-chlorinated alkane. The method according to claim 3, wherein the residual organic solvent contains methylene chloride, chloroform, carbon tetrachloride, ethylene dichloride, ethylene chloride, 2,2,2-trichloroethane, or a mixture thereof. The method according to claim 1, wherein the residual organic solvent contains ethyl acetate. The method according to claim 1, wherein the surfactant comprises sorbitol monostearate, sorbitan monooleate, polyoxyethylene sorbitan monooleate, or a combination thereof. The method according to claim 1, wherein the microparticles are washed with a surfactant-free non-polar alkane, water, or a combination thereof. The method of claim 7, wherein the microparticles are washed with surfactant-free heptane, water, or a combination thereof. The method according to claim 1, wherein the microparticles are collected by screen separation. The method according to claim 1, wherein the microparticles comprise poly (lactide), poly (glycolide), poly (lactide-co-glycolide) or their copolymer, combination or mixture. The method according to any one of claims 1 to 10, wherein

Claims (16)

1. Способ уменьшения содержания остаточного органического растворителя в микрочастицах, включающий:1. A method of reducing the content of residual organic solvent in the microparticles, including: (a) объединение микрочастиц с раствором поверхностно-активного вещества в неполярном алкане для обеспечения дисперсии;(a) combining microparticles with a solution of a surfactant in a non-polar alkane to provide dispersion; (b) смешивание дисперсии;(b) mixing the dispersion; (c) сбор микрочастиц;(c) collecting microparticles; (d) промывание микрочастиц; и(d) washing the microparticles; and (e) сушку микрочастиц;(e) drying the microparticles; где перед стадией (а) микрочастицы содержат по меньшей мере 2% остаточного органического растворителя, содержащего галогенированный растворитель, этилацетат или их смесь.where, before step (a), the microparticles contain at least 2% residual organic solvent containing a halogenated solvent, ethyl acetate or a mixture thereof. 2. Способ по п.1, в котором остаточный органический растворитель содержит С14 галогенированный алкан.2. The method according to claim 1, in which the residual organic solvent contains a C 1 -C 4 halogenated alkane. 3. Способ по п.2, в котором остаточный органический растворитель содержит С14 хлорированный алкан.3. The method according to claim 2, in which the residual organic solvent contains a C 1 -C 4 chlorinated alkane. 4. Способ по п.3, в котором остаточный органический растворитель содержит метиленхлорид, хлороформ, тетрахлорид углерода, этилендихлорид, этиленхлорид, 2,2,2-трихлорэтан или их смесь.4. The method according to claim 3, in which the residual organic solvent contains methylene chloride, chloroform, carbon tetrachloride, ethylene dichloride, ethylene chloride, 2,2,2-trichloroethane or a mixture thereof. 5. Способ по п.1, в котором остаточный органический растворитель содержит этилацетат.5. The method according to claim 1, in which the residual organic solvent contains ethyl acetate. 6. Способ по п.1, в котором поверхностно-активное вещество содержит сорбитола моностеарат, сорбитана моноолеат, полиоксиэтилен сорбитана моноолеат или их комбинацию.6. The method according to claim 1, in which the surfactant contains sorbitol monostearate, sorbitan monooleate, polyoxyethylene sorbitan monooleate, or a combination thereof. 7. Способ по п.1, в котором микрочастицы промывают свободным от поверхностно-активного вещества неполярным алканом, водой или их комбинацией.7. The method according to claim 1, wherein the microparticles are washed with a surfactant-free non-polar alkane, water, or a combination thereof. 8. Способ по п.7, в котором микрочастицы промывают свободным от поверхностно-активного вещества гептаном, водой или их комбинацией.8. The method according to claim 7, in which the microparticles are washed with surfactant-free heptane, water, or a combination thereof. 9. Способ по п.1, в котором микрочастицы собирают посредством ситового сепарирования.9. The method according to claim 1, in which the microparticles are collected by sieve separation. 10. Способ по п.1, в котором микрочастицы содержат поли(лактид), поли(гликолид), поли(лактид-со-гликолид) или их сополимер, комбинацию или смесь.10. The method according to claim 1, in which the microparticles contain poly (lactide), poly (glycolide), poly (lactide-co-glycolide) or their copolymer, combination or mixture. 11. Способ по любому из пп.1-10, в котором микрочастицы содержат биологически активный агент, инкапсулированный в них.11. The method according to any one of claims 1 to 10, in which the microparticles contain a biologically active agent encapsulated in them. 12. Способ по п.11, в котором биологически активный агент является водорастворимым.12. The method according to claim 11, in which the biologically active agent is water soluble. 13. Способ по п.11, в котором биологически активный агент содержит олигопептид.13. The method according to claim 11, in which the biologically active agent contains an oligopeptide. 14. Способ по п.13, в котором биологически активный агент содержит октреотид.14. The method according to item 13, in which the biologically active agent contains octreotide. 15. Способ по п.11, в котором биологически активный агент является по меньшей мере частично растворимым в неполярном алкане.15. The method according to claim 11, in which the biologically active agent is at least partially soluble in non-polar alkane. 16. Способ по п.15, в котором биологически активный агент имеет растворимость, равную по меньшей мере 0,1 мг/мл в неполярном алкане. 16. The method according to clause 15, in which the biologically active agent has a solubility equal to at least 0.1 mg / ml in non-polar alkane.
RU2013119811/05A 2010-09-30 2011-09-28 METHOD FOR REMOVING RESIDUAL ORGANIC SOLVENT FROM MICROPARTICLES RU2013119811A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US38805010P 2010-09-30 2010-09-30
US61/388,050 2010-09-30
PCT/US2011/053655 WO2012044671A2 (en) 2010-09-30 2011-09-28 Method for removing residual organic solvent from microparticles

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RU2013119811A true RU2013119811A (en) 2014-11-10

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EP (1) EP2621473A2 (en)
JP (1) JP5808413B2 (en)
CN (1) CN103370057A (en)
AU (1) AU2011308893B2 (en)
CA (1) CA2813301A1 (en)
IL (1) IL225254A0 (en)
RU (1) RU2013119811A (en)
WO (1) WO2012044671A2 (en)

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CN104382848B (en) * 2014-10-20 2017-04-26 齐鲁制药有限公司 Tacrolimus suspending eye drop liquid and preparation method thereof
CN109718209B (en) * 2017-10-30 2021-03-05 浙江圣兆药物科技股份有限公司 Freeze-drying method of risperidone microspheres with low ethanol residues

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* Cited by examiner, † Cited by third party
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US4637905A (en) * 1982-03-04 1987-01-20 Batelle Development Corporation Process of preparing microcapsules of lactides or lactide copolymers with glycolides and/or ε-caprolactones
AU5741590A (en) 1989-05-04 1990-11-29 Southern Research Institute Improved encapsulation process and products therefrom
PH30995A (en) * 1989-07-07 1997-12-23 Novartis Inc Sustained release formulations of water soluble peptides.
HU221294B1 (en) * 1989-07-07 2002-09-28 Novartis Ag Process for producing retarde compositions containing the active ingredient in a polymeric carrier
US5739265A (en) * 1995-09-20 1998-04-14 Clariant Finance (Bvi) Ltd. Fractionation of phenol formaldehyde condensate and photoresist compositions produced therefrom
US6824822B2 (en) * 2001-08-31 2004-11-30 Alkermes Controlled Therapeutics Inc. Ii Residual solvent extraction method and microparticles produced thereby
WO2005032511A2 (en) * 2003-09-30 2005-04-14 Spherics, Inc. Nanoparticulate therapeutic biologically active agents
US20080317865A1 (en) * 2007-06-20 2008-12-25 Alkermes, Inc. Quench liquids and washing systems for production of microparticles

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WO2012044671A3 (en) 2013-03-14
EP2621473A2 (en) 2013-08-07
AU2011308893A1 (en) 2013-05-09
JP2013538854A (en) 2013-10-17
WO2012044671A2 (en) 2012-04-05
AU2011308893B2 (en) 2015-04-23
IL225254A0 (en) 2013-06-27
CN103370057A (en) 2013-10-23
JP5808413B2 (en) 2015-11-10
CA2813301A1 (en) 2012-04-05

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Effective date: 20160229