| 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. |
