JP4961213B2 - マイクロ粒子の製造方法 - Google Patents
マイクロ粒子の製造方法 Download PDFInfo
- Publication number
- JP4961213B2 JP4961213B2 JP2006550272A JP2006550272A JP4961213B2 JP 4961213 B2 JP4961213 B2 JP 4961213B2 JP 2006550272 A JP2006550272 A JP 2006550272A JP 2006550272 A JP2006550272 A JP 2006550272A JP 4961213 B2 JP4961213 B2 JP 4961213B2
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- JP
- Japan
- Prior art keywords
- eudragit
- microparticles
- mixture
- drug
- medium
- 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.)
- Expired - Fee Related
Links
- 239000011859 microparticle Substances 0.000 title claims abstract description 110
- 238000004519 manufacturing process Methods 0.000 title claims description 15
- 238000000034 method Methods 0.000 claims abstract description 58
- 239000000203 mixture Substances 0.000 claims abstract description 43
- 239000004094 surface-active agent Substances 0.000 claims abstract description 42
- 239000002904 solvent Substances 0.000 claims abstract description 38
- 239000000839 emulsion Substances 0.000 claims abstract description 21
- 230000000975 bioactive effect Effects 0.000 claims abstract description 12
- 238000004945 emulsification Methods 0.000 claims abstract description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- 239000002245 particle Substances 0.000 claims description 42
- 229920000642 polymer Polymers 0.000 claims description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- 229920003134 Eudragit® polymer Polymers 0.000 claims description 14
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 14
- 229940057995 liquid paraffin Drugs 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 11
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 10
- 229960005205 prednisolone Drugs 0.000 claims description 10
- 239000001856 Ethyl cellulose Substances 0.000 claims description 7
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 7
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 7
- 229920001249 ethyl cellulose Polymers 0.000 claims description 7
- TTZKGYULRVDFJJ-GIVMLJSASA-N [(2r)-2-[(2s,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-[(z)-octadec-9-enoyl]oxyethyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1O TTZKGYULRVDFJJ-GIVMLJSASA-N 0.000 claims description 6
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- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 claims description 4
- 239000001593 sorbitan monooleate Substances 0.000 claims description 4
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- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims description 2
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- 229960003515 bendroflumethiazide Drugs 0.000 claims 1
- HDWIHXWEUNVBIY-UHFFFAOYSA-N bendroflumethiazidum Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1=CC=CC=C1 HDWIHXWEUNVBIY-UHFFFAOYSA-N 0.000 claims 1
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- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 13
- 210000001072 colon Anatomy 0.000 description 12
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 description 10
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 10
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- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 9
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- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 6
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- FSXVSUSRJXIJHB-UHFFFAOYSA-M ethyl prop-2-enoate;methyl 2-methylprop-2-enoate;trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CCOC(=O)C=C.COC(=O)C(C)=C.CC(=C)C(=O)OCC[N+](C)(C)C FSXVSUSRJXIJHB-UHFFFAOYSA-M 0.000 description 4
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- 238000004220 aggregation Methods 0.000 description 3
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- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
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- 238000002360 preparation method Methods 0.000 description 3
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- MGYUQZIGNZFZJS-KTKRTIGZSA-N 2-[2-[(z)-octadec-9-enoxy]ethoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCOCCO MGYUQZIGNZFZJS-KTKRTIGZSA-N 0.000 description 2
- IJCWFDPJFXGQBN-RYNSOKOISA-N [(2R)-2-[(2R,3R,4S)-4-hydroxy-3-octadecanoyloxyoxolan-2-yl]-2-octadecanoyloxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCCCCCCCCCCCC IJCWFDPJFXGQBN-RYNSOKOISA-N 0.000 description 2
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- 239000012467 final product Substances 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
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- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 2
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- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
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- 238000004626 scanning electron microscopy Methods 0.000 description 2
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- 230000008685 targeting Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- NMSBTWLFBGNKON-UHFFFAOYSA-N 2-(2-hexadecoxyethoxy)ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCO NMSBTWLFBGNKON-UHFFFAOYSA-N 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
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- 229920003148 Eudragit® E polymer Polymers 0.000 description 1
- 229920003151 Eudragit® RL polymer Polymers 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
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- 150000001298 alcohols Chemical class 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 1
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- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 125000003010 ionic group Chemical group 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
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- 238000002156 mixing Methods 0.000 description 1
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- DNKKLDKIFMDAPT-UHFFFAOYSA-N n,n-dimethylmethanamine;2-methylprop-2-enoic acid Chemical compound CN(C)C.CC(=C)C(O)=O.CC(=C)C(O)=O DNKKLDKIFMDAPT-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- 210000001187 pylorus Anatomy 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- -1 sorbitan fatty acid ester Chemical class 0.000 description 1
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Images
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
- A61K9/14—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
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
-
- 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
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Compounds Of Unknown Constitution (AREA)
- Colloid Chemistry (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0401291A GB0401291D0 (en) | 2004-01-21 | 2004-01-21 | Method of producing microparticles |
| GB0401291.0 | 2004-01-21 | ||
| GB0418141.8 | 2004-08-13 | ||
| GB0418141A GB0418141D0 (en) | 2004-08-13 | 2004-08-13 | Method of producing microparticles |
| PCT/GB2005/000174 WO2005070391A2 (en) | 2004-01-21 | 2005-01-19 | Method of producing microparticles |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007518780A JP2007518780A (ja) | 2007-07-12 |
| JP2007518780A5 JP2007518780A5 (enExample) | 2008-02-28 |
| JP4961213B2 true JP4961213B2 (ja) | 2012-06-27 |
Family
ID=34809878
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006550272A Expired - Fee Related JP4961213B2 (ja) | 2004-01-21 | 2005-01-19 | マイクロ粒子の製造方法 |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US8343545B2 (enExample) |
| EP (1) | EP1722761B1 (enExample) |
| JP (1) | JP4961213B2 (enExample) |
| AT (1) | ATE493116T1 (enExample) |
| DE (1) | DE602005025606D1 (enExample) |
| DK (1) | DK1722761T3 (enExample) |
| WO (1) | WO2005070391A2 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE602005025606D1 (de) * | 2004-01-21 | 2011-02-10 | Univ London Pharmacy | Verfahren zur herstellung von mikroteilchen |
| DE102007009242A1 (de) * | 2007-02-22 | 2008-09-18 | Evonik Röhm Gmbh | Pellets mit magensaftresistenter Wirkstoff-Matix |
| GB201107629D0 (en) * | 2011-05-06 | 2011-06-22 | Proxima Concepts Ltd | Hydrophobic preparations |
| US11654114B2 (en) * | 2017-06-07 | 2023-05-23 | Egy-Nano Pharma, Lp | Oral prolonged drug delivery platforms |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4652641A (en) * | 1984-06-26 | 1987-03-24 | S. C. Mitri | Benzofused lactams useful as antihypertensive agents and as cholecystokinin antagonists |
| FR2618674B1 (fr) * | 1987-07-30 | 1990-06-15 | Ire Celltarg Sa | Microparticules comportant un polymere biodegradable controlant la liberation d'un principe actif antimalarique, compositions pharmaceutiques en comprenant et procede de preparation |
| JP2670680B2 (ja) * | 1988-02-24 | 1997-10-29 | 株式会社ビーエムジー | 生理活性物質含有ポリ乳酸系微小球およびその製造法 |
| JPH04190844A (ja) * | 1990-11-26 | 1992-07-09 | Nippon Kayaku Co Ltd | マイクロカプセルの製法 |
| WO1999000113A1 (en) | 1997-06-27 | 1999-01-07 | Vivorx Pharmaceuticals, Inc. | Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
| US5824638A (en) * | 1995-05-22 | 1998-10-20 | Shire Laboratories, Inc. | Oral insulin delivery |
| FR2769854B1 (fr) * | 1997-10-21 | 2000-03-31 | Prographarm Lab | Nouveau procede d'obtention de microspheres et les produits ainsi realises |
| KR100289471B1 (ko) | 1998-01-19 | 2001-09-17 | 김충섭 | 휀타닐계마취제의이식형서방성제제 |
| US6312712B1 (en) * | 1999-08-26 | 2001-11-06 | Robert R. Whittle | Method of improving bioavailability |
| US6303651B1 (en) * | 1999-09-23 | 2001-10-16 | Thione International, Inc. | Synergistic antioxidant veterinary compositions |
| US6623761B2 (en) * | 2000-12-22 | 2003-09-23 | Hassan Emadeldin M. | Method of making nanoparticles of substantially water insoluble materials |
| US6692771B2 (en) * | 2001-02-23 | 2004-02-17 | Cima Labs Inc. | Emulsions as solid dosage forms for oral administration |
| DE602005025606D1 (de) * | 2004-01-21 | 2011-02-10 | Univ London Pharmacy | Verfahren zur herstellung von mikroteilchen |
-
2005
- 2005-01-19 DE DE602005025606T patent/DE602005025606D1/de not_active Expired - Lifetime
- 2005-01-19 DK DK05701939.0T patent/DK1722761T3/da active
- 2005-01-19 US US10/597,328 patent/US8343545B2/en not_active Expired - Fee Related
- 2005-01-19 EP EP05701939A patent/EP1722761B1/en not_active Expired - Lifetime
- 2005-01-19 WO PCT/GB2005/000174 patent/WO2005070391A2/en not_active Ceased
- 2005-01-19 JP JP2006550272A patent/JP4961213B2/ja not_active Expired - Fee Related
- 2005-01-19 AT AT05701939T patent/ATE493116T1/de active
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2012
- 2012-12-05 US US13/705,928 patent/US20130101646A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20080241251A1 (en) | 2008-10-02 |
| ATE493116T1 (de) | 2011-01-15 |
| WO2005070391A2 (en) | 2005-08-04 |
| JP2007518780A (ja) | 2007-07-12 |
| US20130101646A1 (en) | 2013-04-25 |
| EP1722761B1 (en) | 2010-12-29 |
| US8343545B2 (en) | 2013-01-01 |
| WO2005070391A3 (en) | 2005-09-09 |
| EP1722761A2 (en) | 2006-11-22 |
| DE602005025606D1 (de) | 2011-02-10 |
| DK1722761T3 (da) | 2011-03-28 |
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