依折麦布阿托伐他汀钙片剂的制备  

Preparation of ezetimibe/atorvastatin calcium tablets

作　　者：王艳群[1] 王璐 贺云鹏[1] 杨磊[1] 吴影琪 王东凯[1] WANG Yan-qun WANG Lu HE Yun-peng YANG Lei WU Ying-qi WANG Dong-kai(Shenyang Pharmaceutical University,Shenyang 110016, China Liaoning Center for Certification of Drug, Shenyang 110003, China)

机构地区：[1]沈阳药科大学,沈阳110016 [2]辽宁省药品认证中心,沈阳110003

出　　处：《中国新药杂志》2016年第20期2353-2359,共7页Chinese Journal of New Drugs

摘　　要：目的:制备依折麦布阿托伐他汀钙片,并对影响药物溶出的处方和工艺因素进行考察。方法:采用固体分散技术制备依折麦布层,以聚维酮K30作为载体材料,湿法制粒压片,阿托伐他汀钙层采用粉末直压工艺,通过单因素考察法分别对两层处方进行优化;采用差示扫描量热法(DSC)、X射线衍射法(XRD)、红外光谱法(FTIR)对片剂中依折麦布的存在形式进行表征。结果:最优处方为依折麦布层依折麦布5.8%、乳糖73.2%、聚维酮K30 5.8%、交联羧甲基纤维素钠12%、十二烷基硫酸钠2%、硬脂酸镁1.2%;阿托伐他汀钙层阿托伐他汀钙12.6%、无水乳糖41.6%、微晶纤维素20.8%、羟丙纤维素6%、交联羧甲基纤维素钠6%、碳酸氢钠12%、硬脂酸镁1%;DSC,XRD,FTIR结果显示,依折麦布以无定形或分子状态存在于片剂中。结论:采用该方法可以制备出与市售片剂溶出度相似的依折麦布阿托伐他汀钙片。Objective： To optimize the formulation of ezetimibe /atorvastatin calcium tablets. Methods：Solid dispersion technique and wet granulation tableting were employed to prepare ezetimibe layer. Atorvastatin calcium layer was fabricated by direct powder compression method. The final formulations of the two layers were optimized via single factor tests. Differential scanning calorimetry（ DSC）,powder X-ray diffractometry（ XRD）,and Fourier transform infrared spectroscopy（ FTIR） were carried out to investigate the existence state of ezetimibe in the tablets. Results： The optimized formulation of ezetimibe layer was composed of 5. 8% ezetimibe,73. 2% lactose,5. 8% povidone K30,12% croscarmellose sodium,2% sodium lauryl sulfate,and 1. 2% magnesium stearate. The atorvastatin calcium layer was composed of 12. 6% atorvastatin calcium,41. 6% lactose anhydrous,20. 8%microcrystalline cellulose,6% hydroxypropyl cellulose,6% croscarmellose sodium,12% sodium bicarbonate,and1% magnesium stearate. Ezetimibe existed in the product as amorphous forms or solvates according to the DSC,XRD,and FTIR analysis. Conclusion： The optimized method can obtain ezetimibe / atorvastatin calcium tablets with similar dissolution behavior to commercial products.

关 键 词：依折麦布 阿托伐他汀钙 片剂 固体分散体 溶出度 

分 类 号：R972.6[医药卫生—药品]