硫酸氢氯吡格雷片的制备及其处方工艺优化  

Preparation of Clopidogrel Bisulfate Tablets and Optimization of the Formulation and Technology

作　　者：孙霞[1,2] 王雪[1,2] 郭庆明[1,2] 萧伟[1,2] 

机构地区：[1]江苏康缘药业股份有限公司,江苏连云港222001 [2]中药制药过程新技术国家重点实验室,江苏连云港222001

出　　处：《中国药房》2015年第31期4429-4432,共4页China Pharmacy

摘　　要：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、p H 2.0盐酸盐缓冲液、p H 4.5磷酸盐缓冲液(PBS)、p H 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 preparation 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,p H 2.0 hydrochlorate buffer,p H 4.5 phosphate buffer（PBS）and p H 6.8 PBS were investigated,and influential factor test was conducted. RESULTS：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;accumulative dissolution curves of prepared tablets in 4 kinds of medium were similar to those of Plavix;there were no significant difference 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.

关 键 词：硫酸氢氯吡格雷片 处方 工艺 正交试验 优化 

分 类 号：R943[医药卫生—药剂学]