Process for preparing fine crystalline mixture containing non-steroidal antiphlogistic medicament, fine crystalline mixture prepared in such a manner that, and solid pharmaceutical composition comprising such fine crystalline mixture

摘要

The present invention relates to a process for preparing fine crystalline mixture containing crystals of non-steroidal antiphlogistic medicament with average length up to 145 microns, being selected from the group consisting of derivatives of 2-arylpropionic acid, oxicams or sulfonanilides, in which preparation process a coarse crystalline substance pertaining among non-steroidal antiphlogistic medicaments and being selected from the group consisting of derivatives of 2-arylpropionic acid having a free group -CH(CHi3)COOH or -CHi2CHi2COOH, which substance can also be present in the form of a pharmaceutically acceptable salt, attached directly or through the mediation of a carbonyl functional group to a cyclic system and preferably an aromatic cyclic system, oxicams of the general formula I, in which R represents an aryl or heteroaryl cyclic system, and sulfonanilide nimesulide, is dissolved at a temperature ranging from 35 to 50 degC in an organic solvent being selected from the group consisting of a ketone compound having 3 to 4 carbon atoms, alcohols containing 1 to 4 carbon atoms and a carboxylic compound having 1 to 4 carbon atoms or mixtures thereof. Subsequently the obtained solution is distributed in water containing an auxiliary substance being selected from the group consisting of microcrystalline cellulose, silica and polyvinyl pyrrolidone or mixtures thereof and being cooled to a temperature in the range of 0 to 20 degC, whereupon the product is filtered off and dried. The invention further relates to a fine crystalline mixture of a non-steroidal antiphlogistic medicament being selected from the group consisting of 2-arylpropionic acid, oxicams or sulfonanilides along with an auxiliary substance and prepared by the above-indicated process. The invention also relates to a solid pharmaceutical composition exhibiting significantly improved properties during dissolution and containing 60 to 78 percent by weight of a fine crystalline mixture of a non-steroidal antiphlogistic medicament along with an auxiliary substance according to the present invention, 17 to 40 percent by weight of microcrystalline cellulose, colloidal silica in an amount up to 0.3 percent by weight and a disintegrant in an amount up to 4 percent by weight, optionally a surfactant in an amount up to 0.1 percent by weight. This solid pharmaceutical composition can be filled in pellets or used for preparing tablets.