JP5515198B2 - メコバラミン含有粉体 - Google Patents
メコバラミン含有粉体 Download PDFInfo
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- JP5515198B2 JP5515198B2 JP2007124313A JP2007124313A JP5515198B2 JP 5515198 B2 JP5515198 B2 JP 5515198B2 JP 2007124313 A JP2007124313 A JP 2007124313A JP 2007124313 A JP2007124313 A JP 2007124313A JP 5515198 B2 JP5515198 B2 JP 5515198B2
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- mecobalamin
- powder
- average particle
- particle size
- granules
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- 229960005321 mecobalamin Drugs 0.000 title claims description 73
- 235000007672 methylcobalamin Nutrition 0.000 title claims description 73
- 239000011585 methylcobalamin Substances 0.000 title claims description 73
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 title claims description 73
- 239000000843 powder Substances 0.000 title claims description 27
- 239000002245 particle Substances 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 24
- 239000007787 solid Substances 0.000 claims description 22
- 239000008187 granular material Substances 0.000 description 23
- 239000003826 tablet Substances 0.000 description 20
- 230000000052 comparative effect Effects 0.000 description 14
- 238000010298 pulverizing process Methods 0.000 description 13
- 239000000654 additive Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000008202 granule composition Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose 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
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
メコバラミン含有固形製剤として錠剤を調製するにあたり、その処方例とメコバラミン含有顆粒(A顆粒)の粉砕方法を表1に示す。メコバラミンを含むA顆粒合剤の粉砕については、粉砕能力の異なる3種類の粉砕機を用いた。最も粉砕能力の高い微粉砕ピンミル160Z(商品名:パウレック製)で粉砕したものを比較例1、次いで粉砕能力が高いヤリヤ粉砕機No.4(商品名:ヤリヤ機械製作所製)で粉砕したものを実施例1、最も粉砕能力が低いヤリヤ粉砕機No.2(商品名:ヤリヤ機械製作所製)で粉砕したものを比較例2とした。
主薬及び賦形剤等の成分を表1記載の割合で秤量し、A顆粒及びB顆粒をそれぞれ混合後粉砕した。ここで、A顆粒の粉砕において、比較例1では微粉砕ピンミル160Z、実施例1ではヤリヤ粉砕機No.4、比較例2ではヤリヤ粉砕機No.2を使用した。その後バーチカルグラニュレータ(パウレック製)を用いて、A顆粒はエタノールを造粒用溶媒とし、B顆粒は精製水を造粒用溶媒として撹拌造粒を行い、湿粒を流動層乾燥機にて乾燥した。得られた顆粒をそれぞれ22M篩で整粒し、A顆粒、B顆粒及びステアリン酸マグネシウム等の整顆成分を添加混合した後、ロータリー式打錠機(菊水製作所製)にて、1錠重量を256mgに設定し、錠径8.5mm、2段R面の錠剤を製した。さらにドリアコーター(商品名:パウレック製)を用いてフィルムコーティングを施した。
A顆粒合剤粉砕後のメコバラミンの粒子径を顕微鏡を用いて各ロット100個測定し、その数平均を算出した。
打錠の初期、中期、後期の各過程でサンプリングした各10錠について、メコバラミンの含量均一性試験を行い、30錠でのCV値を評価した。
実施例1並びに比較例1及び2の各錠剤の含水分値を1.0%付近に揃えた上で、65℃で1週間及び2週間経過後のメコバラミンの安定性を評価した。
(1)A顆粒合剤中のメコバラミンの平均粒子径測定
A顆粒中のメコバラミンの平均粒子径は、ピンミルで粉砕した比較例1では14μm、ヤリヤ粉砕機No.4で粉砕した実施例1では32μm、ヤリヤ粉砕機No.2で粉砕した比較例2では50μmであった。メコバラミン原末では54μmであったことから、ヤリヤ粉砕機No.2ではほとんどメコバラミンは粉砕されておらず、一方粉砕能力の最も高いピンミルでは4分の1程度まで小さくなることが判明した。
(2)メコバラミンの含量均一性の確認
結果を表2に示す。
実施例1並びに比較例1及び2のメコバラミン安定性試験の結果を表3に示す。
これまでの結果をまとめると、表4の通りとなる。
Claims (3)
- 被覆されていない平均粒子径が25〜45μmメコバラミンを全体の0.1〜3質量%の割合で粉体内に均一に含有させることを特徴とするメコバラミン含有粉体。
- 請求項1に記載のメコバラミン含有粉体を含有することを特徴とするメコバラミン含有内服用固形製剤。
- 錠剤である請求項2記載のメコバラミン含有内服用固形製剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2007124313A JP5515198B2 (ja) | 2007-05-09 | 2007-05-09 | メコバラミン含有粉体 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2007124313A JP5515198B2 (ja) | 2007-05-09 | 2007-05-09 | メコバラミン含有粉体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008280268A JP2008280268A (ja) | 2008-11-20 |
JP5515198B2 true JP5515198B2 (ja) | 2014-06-11 |
Family
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Application Number | Title | Priority Date | Filing Date |
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JP2007124313A Expired - Fee Related JP5515198B2 (ja) | 2007-05-09 | 2007-05-09 | メコバラミン含有粉体 |
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Country | Link |
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JP (1) | JP5515198B2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9018565B2 (en) | 2010-07-02 | 2015-04-28 | Schott Ag | Generation of holes using multiple electrodes |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104784143A (zh) * | 2014-01-17 | 2015-07-22 | 南京瑞尔医药有限公司 | 一种甲钴胺片组合物 |
CN104122363B (zh) * | 2014-06-24 | 2016-02-24 | 杭州康恩贝制药有限公司 | 一种甲钴胺片有关物质的测定方法 |
CN104473882B (zh) * | 2014-12-25 | 2018-10-02 | 北京华禧联合科技发展有限公司 | 一种甲钴胺颗粒 |
CN105997917A (zh) * | 2016-05-12 | 2016-10-12 | 扬子江药业集团南京海陵药业有限公司 | 一种改良的甲钴胺片及其制备方法 |
CN106236719B (zh) * | 2016-08-30 | 2021-01-19 | 扬子江药业集团南京海陵药业有限公司 | 一种含有甲钴胺的药物组合物及其制备方法 |
CN109820831A (zh) * | 2019-03-26 | 2019-05-31 | 江苏四环生物制药有限公司 | 一种甲钴胺分散片的制粒方法 |
CN111743870A (zh) * | 2020-07-07 | 2020-10-09 | 卓和药业集团有限公司 | 一种甲钴胺分散片的制备方法 |
CN112546003A (zh) * | 2020-12-14 | 2021-03-26 | 卓和药业集团有限公司 | 一种甲钴胺分散片及其制备方法 |
CN114903864B (zh) * | 2022-06-14 | 2023-07-14 | 北京星昊医药股份有限公司 | 一种甲钴胺片及其生产工艺 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA739588B (en) * | 1973-01-18 | 1974-11-27 | Hoffmann La Roche | Stabilized powder |
EP0218679B1 (en) * | 1985-04-16 | 1991-12-11 | Nastech Pharmaceutical Company, Inc. | Aerosol compositions for nasal delivery of vitamin b 12 |
JP2000016940A (ja) * | 1998-04-28 | 2000-01-18 | Takeda Chem Ind Ltd | ビタミンb▲12▼類含有組成物 |
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- 2007-05-09 JP JP2007124313A patent/JP5515198B2/ja not_active Expired - Fee Related
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9018565B2 (en) | 2010-07-02 | 2015-04-28 | Schott Ag | Generation of holes using multiple electrodes |
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JP2008280268A (ja) | 2008-11-20 |
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