JP2006151980A - 微造粒ポリマーの形成方法 - Google Patents
微造粒ポリマーの形成方法 Download PDFInfo
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- JP2006151980A JP2006151980A JP2005342508A JP2005342508A JP2006151980A JP 2006151980 A JP2006151980 A JP 2006151980A JP 2005342508 A JP2005342508 A JP 2005342508A JP 2005342508 A JP2005342508 A JP 2005342508A JP 2006151980 A JP2006151980 A JP 2006151980A
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- poloxamer
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- copolymer
- finely granulated
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- 238000000034 method Methods 0.000 title claims abstract description 45
- 229920000642 polymer Polymers 0.000 title description 10
- 229920001983 poloxamer Polymers 0.000 claims abstract description 81
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims abstract description 76
- 229960000502 poloxamer Drugs 0.000 claims abstract description 66
- 238000007873 sieving Methods 0.000 claims abstract description 11
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract 3
- 239000002245 particle Substances 0.000 claims description 67
- 239000007789 gas Substances 0.000 claims description 33
- 238000005469 granulation Methods 0.000 claims description 24
- 230000003179 granulation Effects 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 22
- 238000002156 mixing Methods 0.000 claims description 19
- 239000012530 fluid Substances 0.000 claims description 18
- 229920001577 copolymer Polymers 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 239000007921 spray Substances 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims description 10
- 229960000623 carbamazepine Drugs 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 9
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 claims description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 5
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 5
- 230000000717 retained effect Effects 0.000 claims description 5
- 239000011148 porous material Substances 0.000 claims description 4
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 3
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 claims description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 3
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 claims description 3
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 claims description 3
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 claims description 3
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 claims description 3
- 229940025084 amphetamine Drugs 0.000 claims description 3
- -1 athenol Chemical compound 0.000 claims description 3
- 229940049706 benzodiazepine Drugs 0.000 claims description 3
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 claims description 3
- 229960004195 carvedilol Drugs 0.000 claims description 3
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 claims description 3
- 229960002327 chloral hydrate Drugs 0.000 claims description 3
- 229960003920 cocaine Drugs 0.000 claims description 3
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 claims description 3
- 229960004166 diltiazem Drugs 0.000 claims description 3
- 229960001797 methadone Drugs 0.000 claims description 3
- 229960001344 methylphenidate Drugs 0.000 claims description 3
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 claims description 3
- 229960002237 metoprolol Drugs 0.000 claims description 3
- 229960000482 pethidine Drugs 0.000 claims description 3
- 229960003209 phenmetrazine Drugs 0.000 claims description 3
- 229960003712 propranolol Drugs 0.000 claims description 3
- 229960004605 timolol Drugs 0.000 claims description 3
- 229960001722 verapamil Drugs 0.000 claims description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims 4
- 239000003570 air Substances 0.000 claims 2
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 claims 2
- 229960000528 amlodipine Drugs 0.000 claims 2
- 229910052786 argon Inorganic materials 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 239000001307 helium Substances 0.000 claims 2
- 229910052734 helium Inorganic materials 0.000 claims 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims 2
- 239000001301 oxygen Substances 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 229940127557 pharmaceutical product Drugs 0.000 claims 2
- OOBHFESNSZDWIU-UHFFFAOYSA-N phenmetrazine Chemical compound CC1NCCOC1C1=CC=CC=C1 OOBHFESNSZDWIU-UHFFFAOYSA-N 0.000 claims 2
- 229940126601 medicinal product Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 4
- 238000005507 spraying Methods 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 3
- 239000002270 dispersing agent Substances 0.000 abstract description 2
- 238000013268 sustained release Methods 0.000 abstract description 2
- 239000012730 sustained-release form Substances 0.000 abstract description 2
- 238000009472 formulation Methods 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 238000009826 distribution Methods 0.000 description 8
- 238000000889 atomisation Methods 0.000 description 7
- 239000000112 cooling gas Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 6
- 229920001992 poloxamer 407 Polymers 0.000 description 6
- 229940044476 poloxamer 407 Drugs 0.000 description 6
- 239000008187 granular material Substances 0.000 description 5
- 238000000227 grinding Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000001000 micrograph Methods 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000007907 direct compression Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 238000007909 melt granulation Methods 0.000 description 3
- 238000003801 milling Methods 0.000 description 3
- 238000002663 nebulization Methods 0.000 description 3
- 229920001993 poloxamer 188 Polymers 0.000 description 3
- 229940044519 poloxamer 188 Drugs 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- 229920005682 EO-PO block copolymer Polymers 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- OOBHFESNSZDWIU-GXSJLCMTSA-N (2s,3s)-3-methyl-2-phenylmorpholine Chemical compound C[C@@H]1NCCO[C@H]1C1=CC=CC=C1 OOBHFESNSZDWIU-GXSJLCMTSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical group O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920002511 Poloxamer 237 Polymers 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 1
- 229960004005 amlodipine besylate Drugs 0.000 description 1
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009506 drug dissolution testing Methods 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000011194 good manufacturing practice Methods 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001021 lactose monohydrate Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000005549 size reduction Methods 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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
- A61K9/20—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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5089—Processes
-
- 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
- B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
- B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
- B01J2/04—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a gaseous medium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
- B29B7/00—Mixing; Kneading
- B29B7/74—Mixing; Kneading using other mixers or combinations of mixers, e.g. of dissimilar mixers ; Plant
- B29B7/7457—Mixing heads without moving stirrer
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
- B29B9/00—Making granules
- B29B9/10—Making granules by moulding the material, i.e. treating it in the molten state
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
- B29B9/00—Making granules
- B29B9/12—Making granules characterised by structure or composition
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
- B29B9/00—Making granules
- B29B9/12—Making granules characterised by structure or composition
- B29B2009/125—Micropellets, microgranules, microparticles
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mechanical Engineering (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
【解決手段】微造粒ポロクサマー粒子の調製方法が開示されている。粒子は、製剤で特別に使用される。この方法は、常圧より高圧の噴霧用ガス、高い噴霧用ガス温度での噴霧ノズルの使用、ポロクサマーの粘度を低減するための高いフィード温度の使用、場合によっては造粒塔でプリルを形成した後の篩い分けを伴う。ポロクサマー粒子は球状であり、好ましくは106ミクロン以下の公称平均粒径を有する。この方法は、非常に費用効果が高く、急速である。
Description
20' ノズル
22 ノズル本体
24 キャップ
24' キャップ
26 ネジリング
28 ネジ山
30 中央流路
34 中央オリフィス
36 外側オリフィス
38 外側流路
40 混合チャンバ
50 ノズル
52 ノズル本体
54 第1流路
56 第2流路
58 第3流路
Claims (22)
- 複数の微造粒ポロクサマー粒子であって、
それぞれが一般式HO(C2H4O)a(C3H6O)b(C2H4O)aH(式中、aの値は約60から約150であり、bの値は約25から約60である)を有する、エチレンオキシドとプロピレンオキシドとの1種または複数のコポリマーを含み、
前記粒子が25℃で球状固体であり、前記複数の粒子が106ミクロン以下の公称平均粒径を有する複数の微造粒ポロクサマー粒子。 - 前記複数の粒子の少なくとも50%が53ミクロン以下の公称平均粒径を有する請求項1に記載の複数の微造粒ポロクサマー粒子。
- 前記1種または複数のコポリマーがそれぞれ約6000〜約18000ダルトンの数平均分子量を有する請求項1に記載の複数の微造粒ポロクサマー粒子。
- 前記1種または複数のコポリマーが、HO(C2H4O)a(C3H6O)b(C2H4O)aH(ただし、aは約80という値を有し、bは約27という値を有する);HO(C2H4O)a(C3H6O)b(C2H4O)aH(ただし、aは約64という値を有し、bは約37という値を有する);HO(C2H4O)a(C3H6O)b(C2H4O)aH(ただし、aは約141という値を有し、bは約44という値を有する);HO(C2H4O)a(C3H6O)b(C2H4O)aH(ただし、aは約101という値を有し、bは約56という値を有する);およびその混合物からなる群から選択される請求項1に記載の複数の微造粒ポロクサマー粒子。
- さらに、医薬品を含む請求項1に記載の複数の微造粒ポロクサマー粒子。
- 前記複数の微造粒ポロクサマー粒子が全重量に対して約10〜約50重量%の量で存在する請求項5に記載の複数の微造粒ポロクサマー粒子。
- 前記医薬品が、カルバマゼピン、メタドン、プロプラノロール、メトプロロール、カルベジロール、チモロール、アテノール、メペリジン、コカイン、アンフェタミン、フェンメトラジン、メチルフェニデート、ジルチアゼム、アムロジピン、ベラパミル、ベンゾジアゼピン、および抱水クロラールからなる群から選択される請求項5に記載の複数の微造粒ポロクサマー粒子。
- 複数の微造粒ポロクサマー粒子の形成方法であって、
a) 一般式HO(C2H4O)a(C3H6O)b(C2H4O)aH(式中、aの値は約60から約150であり、bの値は約25から約60である)を有する、エチレンオキシドとプロピレンオキシドとの少なくとも1種のコポリマーを提供するステップと、
b) ステップa)の少なくとも1種のコポリマーを、その粘度を1300 cps以下に低減するのに十分な温度に加熱するステップと、
c) ステップb)からの加熱された少なくとも1種のコポリマーを噴霧ノズルに通して並流または向流の造粒塔のうちの1つに到達させることによって噴霧化し、それによって前記少なくとも1種のコポリマーの複数の粒子が形成され、前記複数の粒子が公称平均粒径106ミクロン以下を有するステップと、場合によっては
d) ステップc)で形成された前記複数の粒子を篩い分けし、空孔約106ミクロンのメッシュスクリーンを通過した粒子を保持するステップとを含む方法。 - ステップa)が、数平均分子量約6000〜約18000ダルトンを有するエチレンオキシドとプロピレンオキシドとの少なくとも1種のコポリマーを提供するステップを含む請求項8に記載の方法。
- ステップa)が、HO(C2H4O)a(C3H6O)b(C2H4O)aH(ただし、aは約80という値を有し、bは約27という値を有する);HO(C2H4O)a(C3H6O)b(C2H4O)aH(ただし、aは約64という値を有し、bは約37という値を有する);HO(C2H4O)a(C3H6O)b(C2H4O)aH(ただし、aは約141という値を有し、bは約44という値を有する);HO(C2H4O)a(C3H6O)b(C2H4O)aH(ただし、aは約101という値を有し、bは約56という値を有する);およびその混合物からなる群から選択される少なくとも1種のコポリマーを提供するステップを含む請求項8に記載の方法。
- ステップb)が、少なくとも1種のコポリマーを約120℃〜約205℃の温度に加熱するステップを含む請求項8に記載の方法。
- ステップb)が、少なくとも1種のコポリマーを約125℃〜約195℃の温度に加熱するステップを含む請求項8に記載の方法。
- ステップc)が、ステップb)のコポリマーを、二流体噴霧ノズルまたは三流体噴霧ノズルのうちの1つに通すステップを含む請求項8に記載の方法。
- ノズルを二流体噴霧ノズルとなるように選択し、外側ガスの圧力を約100〜約150psigに設定する請求項13に記載の方法。
- 外側ガスを約80〜約140℃の温度に設定するステップをさらに含む請求項14に記載の方法。
- 外側ガスが、窒素、空気、酸素、ヘリウム、およびアルゴンからなる群から選択される請求項14に記載の方法。
- ステップd)で保持された粒子を医薬品と混合するステップをさらに含む請求項8に記載の方法。
- 粒子を全重量に対して10〜50重量%の量で混合するステップを含む請求項17に記載の方法。
- カルバマゼピン、メタドン、プロプラノロール、メトプロロール、カルベジロール、チモロール、アテノール、メペリジン、コカイン、アンフェタミン、フェンメトラジン、メチルフェニデート、ジルチアゼム、アムロジピン、ベラパミル、ベンゾジアゼピン、および抱水クロラールからなる群から、医薬品を選択するステップを含む請求項17に記載の方法。
- ノズルを三流体噴霧ノズルとなるように選択し、内側ガスの圧力を約100〜約150psigに設定し、外側ガスの圧力を約100〜約150psigに設定する請求項13に記載の方法。
- 内側ガスと外側ガスとを約80〜約140℃の温度に設定するステップをさらに含む請求項20に記載の方法。
- 内側ガスと外側ガスとが、窒素、空気、酸素、ヘリウム、およびアルゴンからなる群から選択される請求項20に記載の方法。
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JP4903424B2 (ja) | 2012-03-28 |
US9149433B2 (en) | 2015-10-06 |
US20150374629A1 (en) | 2015-12-31 |
US20060115535A1 (en) | 2006-06-01 |
EP1661558A1 (en) | 2006-05-31 |
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