Preparation Method Of The Solid Formulation Of Clopidogrel Bisulfate

Abstract

A solid formulation of clopidogrel bisulfate and its preparation method are disclosed. The formulation comprises clopidogrel bisulfate as active ingredient, colloidal silicon dioxide as anti-adherent/coating and the carriers selected from diluent, binder, glidant, disintegrant and/or lubricant.

1 . A premix granule of Clopidogrel bisulfate characterized in that the premix granule comprises: Clopidogrel bisulfate and Colloidal Silicon Dioxide for covering Clopidogrel bisulfate, wherein the weight of Colloidal Silicon Dioxide is 0.5%-10% w/w of that of Clopidogrel bisulfate, wherein the average particle size of Clopidogrel bisulfate is 10-100 μm. 
     
     
         2 . The premix granule of Clopidogrel bisulfate of  claim 1 , characterized in that the weight of Colloidal Silicon Dioxide is 1.0%-5% w/w of that of Clopidogrel bisulfate. 
     
     
         3 . The premix granule of Clopidogrel bisulfate of  claim 1 , characterized in that the weight of both Colloidal Silicon Dioxide and Clopidogrel bisulfate are 90%-100% w/w of that of the premix granule. 
     
     
         4 . The premix granule of Clopidogrel bisulfate of  claim 1 , characterized in that the premix granule is prepared by the following method: Colloidal Silicon Dioxide and Clopidogrel bisulfate are mixed to form the premix granule. 
     
     
         5 . A pharmaceutical composition of Clopidogrel bisulfate, characterized in that the composition contains the premix granule of Clopidogrel bisulfate in accordance with  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         6 . The pharmaceutical composition of  claim 4 , characterized in that the composition is a solid formulation. 
     
     
         7 . The pharmaceutical combination of  claim 4 , characterized in that the composition is an oral tablet dosage form. 
     
     
         8 . The pharmaceutical composition of  claim 4 , characterized in that the composition contains Clopidogrel bisulfate as an active ingredient, Colloidal Silicon Dioxide as an anti-adherent/coating agent, and the carrier selected form the following group: diluent, binder, glidant, disintegrant and/or lubricant. 
     
     
         9 . The pharmaceutical composition of  claim 4 , characterized in that the composition is an oral tablet dosage form and contains the following ingredients:
 25-50 weight % Clopidogrel bisulfate,   1-4 weight % Colloidal Silicon Dioxide as an anti-adherent/covering agent,   20-30 weight % Lactose and 10-30 weight % Mcrocrystalline cellulose,   0.6-1.5 weight % Hydroxypropyl Cellulose,   0.2-0.5 weight % Colloidal Silicon Dioxide as a glidant,   1.2-4.0 weight % Crospovidone   
     
     
         10 . The pharmaceutical composition of  claim 4 , characterized in that the composition is prepared by the following steps:
 (a) Mixing Colloidal Silicon Dioxide and Clopidogrel bisulfate to form the premix granule;   (b) Mixing the premix granule obtained from step (a) with diluents, then adding alcohol solution of binder for wet granulation to obtain the wet granule;   (c) Drying and screening the wet granule obtained from step (b) to obtain dry granule;   (d) Mixing the dry granule obtained from step (c) and glidant, disintegrant and lubricants, then compressing to obtain Clopidogrel bisulfate tablet; and   (e) Optionally coating the tablet obtained from step (d) to obtain the film-coated final tablet.   
     
     
         11 . A method for preparing pharmaceutical composition of Clopidogrel bisulfate, comprising the step of:
 (a) Mixing Colloidal Silicon Dioxide and Clopidogrel bisulfate to form the premix granule;   (b) Mixing the premix granule obtained from step (a) with diluents, then adding alcohol solution of binder for wet granulation to obtain the wet granule;   (c) Drying and screening the wet granule obtained from step (b) to obtain dry granule;   (d) Mixing the dry granule obtained from step (c) and glidant, disintegrant and lubricants, then compressing to obtain Clopidogrel bisulfate tablet; and   (e) Optionally coating the tablet obtained from step (d) to obtain the film-coated final tablet.