1. Department of Pharmaceutics, East China University of Science and Technology, Shanghai 200237, China; 2. Department of Pharmaceutics Research Center, SINE Pharmacy, Shanghai 201203, China
Abstract��
OBJECTIVE To investigate the formulation and process for preparing stable clopidogrel bisulfate tablets (Form I by elucidating the critical formulation and in-process parameters affecting critical granule properties, in order to solve sticking problems in tablet processing as well as improving stability under storage. METHODS Drug-excipient interactions were evaluated, and different dry granulations such as direct compression, melt granulation and roller compaction were compared, in terms of impurity levels, tablet properties and in vitro dissolution. RESULTS The stability of free clopidogrel bisulfate was liable to the high moisture, strong light and elevated temperature. Compared with direct compression and roller compaction, melt granulation was more suitable to prepare clopidogrel bisulfate tablet. Sodium stearyl fumarate avoided sticking problem in tablet processing with PEG 6000. Comparable dissolution profiles were obtained and similar to that of Pavix of Sinofi, with the similar factors above 50. Furthermore, the accelerated stability test suggested that tablets prepared by melt granulation under storage at 40 C and 75% RH for 3 months were stable and showed good physicochemical properties. CONCLUSION The CPG tablets were stable and the established processes were simple and reproducible.