TWI556823B - 含阿卡波糖之口崩解錠 - Google Patents
含阿卡波糖之口崩解錠 Download PDFInfo
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- TWI556823B TWI556823B TW100114368A TW100114368A TWI556823B TW I556823 B TWI556823 B TW I556823B TW 100114368 A TW100114368 A TW 100114368A TW 100114368 A TW100114368 A TW 100114368A TW I556823 B TWI556823 B TW I556823B
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- acarbose
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- 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
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
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- 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
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- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- 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
- A61K9/204—Polyesters, e.g. poly(lactide-co-glycolide)
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- 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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- 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
- A61K9/2095—Tabletting processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
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Description
本發明的一目的係提供一種用於葡糖苷酶抑制劑阿卡波糖的口服崩解錠(ODT)。以含1~30%阿卡波糖和40~90%水溶性載劑的口服分解錠可達成此目的。為獲得所欲性質，其成分必需與一不溶性潤滑劑預壓製及與一水不溶性載劑預拌和。
作為抗糖尿病之葡糖苷酶抑制劑的最適作用有賴於儘可能均勻分佈活性成分於吞服食物內的助益。藉由口服崩解錠之助可達到此均勻分佈的目的。該錠劑和活性成分溶解於口腔內，然後活性成分以溶液的狀態吞入而使該吞服食物於胃內形成易分佈於其中的溶液。
由於活性成分的物理性質形成形成難且緩慢溶解的錠劑，不易製備該阿卡波糖活性成分的口服崩解錠。當錠劑內含有大量(<50%)的水不溶性載劑時可獲得速溶性口服崩解錠。然而，由於該大部份的不溶性賦形劑於舌頭上被感覺成粗糙的異物感而使這些錠劑產生無法被接受的口感。
因此本發明的發展工作著重於具有低水溶比例的調配物。
藉由選擇適當的賦形劑及適當的製程(阿卡波糖的預壓製)可使調配物具有極佳的口感並且迅速被釋出。
藉由下述及相關製程的配製方法可達到此目的。
本發明調配物係一種含有1~30%阿卡波糖和40~90%水溶性載劑的口服崩解錠。其崩解時間低於60秒，較佳為低於45秒，更佳為低於30秒，又更佳為低於20秒。該水溶性載劑係產品。下列為的組成：90%甘露糖醇、5%交聯聚維酮和5%的聚醋酸乙烯。同樣，可與混合物內的任選黏合劑：甘露糖醇、異麥芽糖醇、山梨糖醇、乳糖、澱粉、改性澱粉和麥芽糖糊精被用作為水溶性載劑。就其性質和速溶性而言，重要的是口服可崩解錠之整體濕度為介於0~8%，較佳為介於1~5%。該錠劑具有低於1%的磨擦力及介於20~50N，較佳為介於25~45N的斷裂強度。製錠前，該阿卡波糖被製成100至800 μm，較佳為100~600 μm的平均粒度。
在第一製備步驟中，以潤滑劑顆粒化阿卡波糖；然後以諸如Avicel之微晶纖維素混合該粒化物質。較佳為藉由乾造粒法進行粒化。就此目的而言，較佳為使用輾壓機之模式，其中粉末通過兩支旋轉輥間之定距窄縫計量，並僅藉由壓力壓實而形成平坦、延伸鏈之股，已知為條帶。這些條帶於其後步驟中必需被縮小尺寸而使其能直接被計量入製錠機內。該壓製的平均粒徑較佳為介於100和800 μm之間，較佳為介於100~600 μm之間。該壓製物最佳為至少15%具有>250 μm的粒徑。
在進一步摻混賦形劑之後，從製錠機製備含有1~30%阿卡波糖、40~90%水溶性載劑和1~50%水不溶性載劑的口服崩解錠。藉由預壓製該阿卡波糖及其後摻混該成分可減小用於分解阿卡波糖和賦形劑之間所需的接觸面積。因此，依此方法製備的錠劑具有低於60秒，較佳為低於45秒，更佳為低於30秒，又更佳為低於20秒的崩解時間。該口服崩解錠的整體濕度為介於0和8%，較佳為介於1和5%之間。本發明亦係關於一種製備含阿卡波糖和賦形劑之口服崩解錠的方法，其步驟包括：
(1) 預壓製阿卡波糖；
(2) 混合水不溶性載劑，諸如微晶纖維素；
(3) 混合水溶性載劑，且隨繼
(4) 製成錠劑。
可視需要結合第2和3步驟。
所使用的阿卡波糖具有介於0和5%，較佳為介於1和4%的水含量。阿卡波糖壓製物的平均粒徑較佳為介於1和200 μm之間。該錠劑具有低於1%的磨擦力及具有介於10~50 N，較佳為介於15~45 N之間的斷裂強度。該阿卡波糖壓製物最佳為至少15%具有>250 μm的粒徑。
全部的調配物常以非純化阿卡波糖與水溶性填充料共同加工。使用純的形式時常會被製成硬質錠劑。在中間步驟中藉由以Avicel包裹，加入水溶性填充料亦可使錠劑迅速崩解。水溶性填充料的一項優點為使調配物具有較佳的口感，以及在錠劑的崩解時間上亦具有較佳的安定性。該錠劑的特徵為具有至少兩年，較佳為三年的安定性。
Claims (6)
- 一種口服崩解錠劑，其含有：a)1~30%預壓製阿卡波糖，其具有100至800μm的平均粒徑以及具有介於0和5%間的含水量(moisture content)，且15%之顆粒具有>250μm之粒徑，b)40~90%水溶性載劑，其係由下列組成：90%甘露糖醇、5%交聯聚維酮和5%聚醋酸乙烯，和c)1~50%水不溶性載劑，其為微晶纖維素。
- 如申請專利範圍第1項之錠劑，其含有具有100至600μm之平均粒徑的預壓製阿卡波糖。
- 如申請專利範圍第1或2項之錠劑，其具有低於60秒的崩解時間。
- 一種製備如申請專利範圍第1至3項中任一項之含阿卡波糖之口服崩解錠劑的方法，其包括下列步驟：(a)預壓製阿卡波糖，以得到具有100至800μm的平均粒徑，且15%之顆粒具有>250μm之粒徑；(b)混合水不溶性載劑；(c)混合水溶性載劑； (d)製成錠劑，其特徵為使用具有介於0和5%間之含水量的阿卡波糖。
- 如申請專利範圍第4項之方法，其特徵為使用具有100至600μm之平均粒徑的阿卡波糖。
- 如申請專利範圍第1或2項之口服崩解錠劑，其被用於治療糖尿病。
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10161114 | 2010-04-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201141490A TW201141490A (en) | 2011-12-01 |
| TWI556823B true TWI556823B (zh) | 2016-11-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW100114368A TWI556823B (zh) | 2010-04-27 | 2011-04-26 | 含阿卡波糖之口崩解錠 |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US20130131003A1 (zh) |
| EP (1) | EP2563329B1 (zh) |
| JP (1) | JP5944378B2 (zh) |
| KR (1) | KR101788350B1 (zh) |
| CN (2) | CN106924199A (zh) |
| AU (1) | AU2011247642C1 (zh) |
| BR (1) | BR112012027303A2 (zh) |
| CA (1) | CA2797365A1 (zh) |
| CL (1) | CL2012003011A1 (zh) |
| CO (1) | CO6640213A2 (zh) |
| CR (1) | CR20120548A (zh) |
| CU (1) | CU20120152A7 (zh) |
| DO (1) | DOP2012000277A (zh) |
| EC (1) | ECSP12012279A (zh) |
| ES (1) | ES2623025T3 (zh) |
| GT (1) | GT201200290A (zh) |
| IL (1) | IL222368B (zh) |
| MX (1) | MX348865B (zh) |
| MY (1) | MY179724A (zh) |
| NZ (1) | NZ603199A (zh) |
| PE (1) | PE20130403A1 (zh) |
| PH (1) | PH12012502139A1 (zh) |
| SG (2) | SG184851A1 (zh) |
| SI (1) | SI2563329T1 (zh) |
| TW (1) | TWI556823B (zh) |
| UA (1) | UA111155C2 (zh) |
| WO (1) | WO2011134962A2 (zh) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TR201100150A2 (tr) * | 2011-01-06 | 2012-07-23 | Bi̇lgi̇ç Mahmut | Suda çözünür dozaj formları |
| WO2013115741A1 (en) * | 2012-01-31 | 2013-08-08 | Mahmut Bilgic | Pharmaceutical compositions comprising alpha-glucosidase inhibitor |
| WO2013115738A1 (en) * | 2012-01-31 | 2013-08-08 | Mahmut Bilgic | Micronized acarbose |
| WO2014036528A2 (en) | 2012-08-31 | 2014-03-06 | Ixchel Pharma, Llc | Agents useful for treating obesity, diabetes and related disorders |
| CN104013590A (zh) * | 2014-05-09 | 2014-09-03 | 万特制药(海南)有限公司 | 一种含阿卡波糖的药物组合物及其制备方法 |
| PL3233066T3 (pl) * | 2014-12-17 | 2022-02-14 | Empros Pharma Ab | Kompozycja o zmodyfikowanym uwalnianiu orlistatu i akarbozy do leczenia otyłości i powiązanych z nią zaburzeń metabolicznych |
| CN105213341A (zh) * | 2015-10-29 | 2016-01-06 | 无锡福祈制药有限公司 | 一种阿卡波糖片及其制备方法 |
| CN113081984B (zh) * | 2021-04-19 | 2023-06-02 | 北京阳光诺和药物研究股份有限公司 | 一种阿卡波糖口崩片及其制备方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060119261A1 (en) * | 2004-12-06 | 2006-06-08 | Lg Electronics Inc. | Organic electroluminescent device |
| US20090129620A1 (en) * | 2006-02-27 | 2009-05-21 | Junichi Tagawa | Wearable terminal, mobile imaging sound collecting device, and device, method, and program for implementing them |
| WO2009071219A2 (en) * | 2007-12-08 | 2009-06-11 | Bayer Schering Pharma Aktiengesellschaft | Oral dispersable tablet |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3134591A1 (de) * | 1981-09-01 | 1983-03-10 | Bayer Ag, 5090 Leverkusen | Neue arzneimittelpraeparationen fuer glykosidhydrolasen-inhibitoren |
| JPH10182687A (ja) * | 1996-10-21 | 1998-07-07 | Bayer Yakuhin Kk | アカルボースの貯蔵安定化法 |
| DE19802700A1 (de) * | 1998-01-24 | 1999-07-29 | Bayer Ag | Verfahren zur Herstellung einer im Mund schnell zerfallenden Arzneiform, die als Wirkstoff Acarbose enthält |
| US20040081697A1 (en) * | 1998-11-12 | 2004-04-29 | Smithkline Beecham P.L.C. | Pharmaceutical composition for modified release of an insulin sensitiser and another antidiabetic agent |
| US20060229261A1 (en) * | 2005-04-12 | 2006-10-12 | John Devane | Acarbose methods and formulations for treating chronic constipation |
| MY157620A (en) * | 2006-01-31 | 2016-06-30 | Cytochroma Dev Inc | A granular material of a solid water-soluble mixed metal compound capable of binding phosphate |
| FI20070521L (fi) * | 2006-11-10 | 2008-05-11 | Atacama Labs Oy | Rakeita, tabletteja ja rakeistusmenetelmä |
| CN101411715B (zh) * | 2007-10-19 | 2012-03-28 | 杭州华东医药集团生物工程研究所有限公司 | 含有阿卡波糖的药物组合物 |
| JP5291324B2 (ja) * | 2007-11-01 | 2013-09-18 | 沢井製薬株式会社 | 口腔内崩壊錠 |
| JP2009114113A (ja) * | 2007-11-06 | 2009-05-28 | Nipro Corp | 口腔内崩壊錠及びその製造方法 |
| CN101925349A (zh) * | 2007-12-21 | 2010-12-22 | 欧兰德股份有限公司 | 替马西泮的口腔崩解片组合物 |
| TR201808694T4 (tr) * | 2008-06-20 | 2018-07-23 | Merck Patent Gmbh | Doğrudan sıkıştırılabilen ve hızlı parçalanan tablet matrisi. |
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2011
- 2011-04-26 TW TW100114368A patent/TWI556823B/zh not_active IP Right Cessation
- 2011-04-26 CA CA2797365A patent/CA2797365A1/en not_active Abandoned
- 2011-04-26 CN CN201610934162.1A patent/CN106924199A/zh active Pending
- 2011-04-26 SG SG2012076147A patent/SG184851A1/en unknown
- 2011-04-26 UA UAA201213526A patent/UA111155C2/uk unknown
- 2011-04-26 SG SG10201505844WA patent/SG10201505844WA/en unknown
- 2011-04-26 PH PH1/2012/502139A patent/PH12012502139A1/en unknown
- 2011-04-26 AU AU2011247642A patent/AU2011247642C1/en not_active Ceased
- 2011-04-26 KR KR1020127028046A patent/KR101788350B1/ko not_active Expired - Fee Related
- 2011-04-26 EP EP11716264.4A patent/EP2563329B1/en not_active Not-in-force
- 2011-04-26 WO PCT/EP2011/056587 patent/WO2011134962A2/en not_active Ceased
- 2011-04-26 ES ES11716264.4T patent/ES2623025T3/es active Active
- 2011-04-26 CN CN2011800205487A patent/CN102905687A/zh active Pending
- 2011-04-26 MY MYPI2012700818A patent/MY179724A/en unknown
- 2011-04-26 NZ NZ603199A patent/NZ603199A/en not_active IP Right Cessation
- 2011-04-26 JP JP2013506633A patent/JP5944378B2/ja not_active Expired - Fee Related
- 2011-04-26 PE PE2012002079A patent/PE20130403A1/es not_active Application Discontinuation
- 2011-04-26 US US13/643,929 patent/US20130131003A1/en not_active Abandoned
- 2011-04-26 SI SI201131170A patent/SI2563329T1/sl unknown
- 2011-04-26 MX MX2012012459A patent/MX348865B/es active IP Right Grant
- 2011-04-26 BR BR112012027303A patent/BR112012027303A2/pt not_active IP Right Cessation
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2012
- 2012-10-11 IL IL222368A patent/IL222368B/en active IP Right Grant
- 2012-10-25 CU CU2012000152A patent/CU20120152A7/es unknown
- 2012-10-26 GT GT201200290A patent/GT201200290A/es unknown
- 2012-10-26 EC ECSP12012279 patent/ECSP12012279A/es unknown
- 2012-10-26 CL CL2012003011A patent/CL2012003011A1/es unknown
- 2012-10-26 DO DO2012000277A patent/DOP2012000277A/es unknown
- 2012-10-26 CR CR20120548A patent/CR20120548A/es unknown
- 2012-10-26 CO CO12192234A patent/CO6640213A2/es not_active Application Discontinuation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060119261A1 (en) * | 2004-12-06 | 2006-06-08 | Lg Electronics Inc. | Organic electroluminescent device |
| US20090129620A1 (en) * | 2006-02-27 | 2009-05-21 | Junichi Tagawa | Wearable terminal, mobile imaging sound collecting device, and device, method, and program for implementing them |
| WO2009071219A2 (en) * | 2007-12-08 | 2009-06-11 | Bayer Schering Pharma Aktiengesellschaft | Oral dispersable tablet |
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