目的:制备硫酸氢氯吡格雷片并优化其处方工艺.方法:采用单因素试验联合相容性试验对片剂的填充剂、崩解剂、黏合剂、润滑剂和制备方法进行筛选;以黏冲情况和崩解时间的综合评分为指标,采用正交试验优选崩解剂[低取代羟丙基纤维素(L-HPC)]、润滑剂(氢化植物油和聚乙二醇6000)的用量,并进行验证;考察所制片剂与进口制剂(波立维)在水、pH 2.0盐酸盐缓冲液、pH 4.5磷酸盐缓冲液(PBS)、pH 6.8 PBS中的溶出情况并进行影响因素试验.结果:采用干法制粒,最优处方(1 000片)为硫酸氢氯吡格雷97.8 g、甘露醇84 g、预胶化淀粉36 g、L-HPC 8 g、氢化植物油8 g、聚乙二醇6000 6 g;所制片剂压片无黏冲现象且崩解时间适中,其与波立维在4种溶出介质中溶出曲线均相似;影响因素试验结果与波立维比较无明显差异.结论:成功制得硫酸氢氯吡格雷片,且处方合理、工艺可行、质量稳定可控.%OBJECTIVE:To prepare Clopidogrel bisulfate tablets,and to optimize its formulation and technology. METHODS:The single factor test and compatibility test were used to optimize the fillers,disintegrating agents,adhesive,lubricants and prepa-ration technology;using sticking situation and disintegration time as indexes,the orthogonal test was used to optimize the amount of disintegrating agents [low substituted hydroxypropyl cellulose(L-HPC)],lubricants(hydrogenated vegetable oil and PEG6000), and the optimal technology was validated. The dissolution of prepared tablet and imported tablet(Plavix)in water,pH 2.0 hydro-chlorate buffer,pH 4.5 phosphate buffer(PBS)and pH 6.8 PBS were investigated,and influential factor test was conducted. RE-SULTS:Clopidogrel bisulfate tablets were prepared with dry granulating. The optimal formulation (1 000 tablets) was as follows as clopidogrel bisulfate 97.8 g,mannitol 84 g,amylum pregelatinisatum 36 g,L-HPC 8 g,hydrogenated vegetable oil 8 g, PEG6000 6 g;no tablet compressing sticking situation was found in prepared tablets and it owned medium disintegration time;ac-cumulative dissolution curves of prepared tablets in 4 kinds of medium were similar to those of Plavix;there were no significant dif-ference in results of influential factor test between prepared tablet and Plavix. CONCLUSIONS:Clopidogrel bisulfate tablets are prepared successfully,and the formulation is reasonable,practical,stable and controllable in quality.
展开▼
