公开(公告)号：US20150366825A1

公开(公告)日：2015-12-24

申请号：US14764804

申请日：2013-04-25

申请人： Shraddha Sanjeev JOSHI ,  Ashish Sharadchandra GUHA ,  Suresh Shahuraj DOKE ,  Ashishkumar Prafulchandra SHAH ,  Preeti PATIL

发明人： Shraddha Sanjeev JOSHI ,  Ashish Sharadchandra GUHA ,  Suresh Shahuraj DOKE ,  Ashishkumar Prafulchandra SHAH ,  Preeti PATIL

IPC分类号： A61K31/138 ,  A61K9/00 ,  A61K9/48 ,  A61K9/50 ,  A61K9/20

CPC分类号： A61K31/138 ,  A61K9/009 ,  A61K9/2054 ,  A61K9/2081 ,  A61K9/2095 ,  A61K9/4808 ,  A61K9/4833 ,  A61K9/5026 ,  A61K9/5047 ,  A61K9/5084

摘要： Multiparticulate pharmaceutical composition comprising a multitude of two kinds of pellets, A and B, each comprising metoprolol or a pharmaceutically acceptable salt thereof as an active pharmaceutical ingredient, wherein the pellets A are coated with a coating layer comprising at least 30% by weight of a polymeric compound consisting of one or more (meth)acrylate copolymers polymerized from 20 to 40% by weight of ethyl acrylate, 60 to 80% by weight of methyl methacrylate and 0 or less than 5% by weight of methacrylic acid or acrylic acid, in an amount sufficient to result in an active pharmaceutical ingredient release profile according to USP in pH 6.8 test medium with a release rate of less than 20% after 4 hours, wherein the pellets B are not coated or coated with a coating layer and show an active pharmaceutical ingredient release profile according to USP in pH 6.8 test medium with an active pharmaceutical ingredient release rate of more than 40% after 4 hours, wherein the metoprolol release rate of the pellets A in pH 1.2 test medium according to USP with the addition of 40% (v/v) ethanol is •not more than 15% after 15 minutes •more than 15 up to 40% after 30 minutes, wherein the metoprolol release rate of the pellets B in pH 1.2 test medium according to USP with the addition of 40% (v/v) ethanol is •more than 15% after 15 minutes •more than 40% after 30 minutes and wherein the pellets A and B are present in the multiparticulate pharmaceutical composition in a relation resulting in a combined active pharmaceutical ingredient release profile of the multiparticulate pharmaceutical composition according to USP in pH 6.8 test medium with releases rates of •not more than 25% after 1 hour •20 to 40% after 4 hours •40 to 60% after 8 hours •not less than 80% after 20 hours.

摘要翻译： 包含多种两种丸剂A和B的多片剂药物组合物，A和B各自包含美托洛尔或其药学上可接受的盐作为活性药物成分，其中颗粒A涂覆有包含至少30重量％ 由一种或多种（甲基）丙烯酸酯共聚物组成的高分子化合物，其由20至40重量％的丙烯酸乙酯，60至80重量％的甲基丙烯酸甲酯和0或小于5重量％的甲基丙烯酸或丙烯酸聚合， 足以导致根据USP在pH 6.8测试培养基中具有活性药物成分释放曲线的量，其中4小时后释放速率小于20％，其中颗粒B未涂覆或涂覆有涂层并显示活性物质 根据USP在pH 6.8测试培养基中的药物成分释放曲线，4小时后活性药物成分释放速率大于40％，其中美托洛尔 在加入40％（v / v）乙醇的根据USP的pH 1.2测试培养基中的丸粒A的释放速率为15分钟后不超过15％•30分钟后超过15％至40％，其中 在加入40％（v / v）乙醇的根据USP的pH 1.2测试培养基中的丸粒B的美托洛尔释放速率为15分钟后超过15％•30分钟后超过40％，并且其中颗粒A 和B以多颗粒药物组合物的形式存在，其导致根据USP在pH 6.8测试培养基中的多颗粒药物组合物的组合的活性药物成分释放曲线，1小时后释放速率为不超过25％•20至 4小时后40％•8小时后40-60％•20小时后不少于80％。