Amorphous pharmaceutical composition based on ezetimibe and simvastatin and the method of its preparation

摘要

The subject of the notification is physically stable, both under the standard storage conditions and under the conditions of manufacture, the amorphous pharmaceutical composition based on ezetimib and simvastatin. The composition consists of a triplamoramoramoramoramorphocomplex complex complex consisting of the ezetimibu((3R,4S)-1-(4-fluorophophenyl)-3-[[(3S)-3-(4-fluorophphenyl)-3-hydrohydroproppropproppropyl]-4-(4-hydroxhydroxxyphenyl)azerid2-2-one) of the model 1, the simwasstatistatin (1,2,2,2,3,8,8,8,8,8,8,8,8,8,8,8,8,8,8,8,8,8,8,8,8,8,3,3,8,3,3,3,3,3,3,3,3,3,3,3,3,3,3,3,3,3,3,3,3,3,3,3-yl)-ethyl]-1-naphthalenyl acid 2, 2-Dimethyl butanol) having a formula 2, and a copolymer of vinyl pyrrolidone and vinyl acetate having a formula 3,is the molecular weight of the molecular molar copolymer of division 45000 -70000 g/mol, the weight ratio of ezetimib to simvastatin being from 1:1 to 1:8, and the proportion of the copolymer to the ezetimib + simvastatin system is between 5 -85 wt.%. In addition, the scope of the notification is also how to obtain amorphous formulation of the pharmaceutical formulation based on ezetimib and simvastatin, namely that crystalline pharmaceutical substances in the form of ezetimib and simvastatin, as well as vinylpyrrolidone and vinyl acetate copolymer, of molecular molecular weight copolymer from the range 45000 - 70000 g/mol,in proportions such that the mass ratio of ezetimib to simvastatin is from 1:1 to 1:8, while the proportion of the copolymer to ezetimib + simvastatin is from 5 to 85 wt.%,connecting,until a homogeneous mixture is obtained, which is then melted in a temperature range from 100'c to 180'c, and the temperature in the case in question is taken from the range indicated so as to be, system melting temperatures, after which the resulting homogeneous mixture is rapidly cooled to a temperature below the point of transition of the glass triple amorphous system of ezetimib + simvastatin + copolymer.