MULTIPARTICULATE PHARMACEUTICAL COMPOSITION COMPRISING A MULTITUDE OF TWO KINDS OF PELLETS

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.

主权项

1. A multiparticulate pharmaceutical composition comprising a multitude of pellets A and pellets B, each of the pellets A and the pellets B comprising metoprolol or a pharmaceutically acceptable salt thereof as an active pharmaceutical ingredient,
wherein the pellets A are coated with a first coating layer that is 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, the first coating layer comprising at least 30% by weight of a polymeric compound, and the 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, wherein the pellets B are optionally coated with a second 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 pellets A have a metoprolol release rate, in a pH 1.2 test medium according to USP with addition of 40% (v/v) ethanol, of
not more than 15% after 15 minutesmore than 15% and up to 40% after 30 minutes, wherein the pellets B have a metoprolol release rate, in a pH 1.2 test medium according to USP with addition of 40% (v/v) ethanol, of
more than 15% after 15 minutesmore than 40% after 30 minutes and wherein the pellets A and the pellets B are present in the multiparticulate pharmaceutical composition in a relation that results in a combined active pharmaceutical ingredient release profile of the multiparticulate pharmaceutical composition according to USP in a pH 6.8 test medium with release rates of
not more than 25% after 1 hour20% to 40% after 4 hours40% to 60% after 8 hoursnot less than 80% after 20 hours.