超临界CO2抗溶剂法制备依折麦布颗粒  

Preparation of Ezetimibe by supercritical CO2 anti-solvent process

作　　者：张卓 李庆领[1] 郝贵周 曹荣凯 郝明洁 胡德栋[1,2,3] ZHANG Zhuo;LI Qingling;HAO Guizhou;CAO Rongkai;HAO Mingjie;HU Dedong(Electromechanical Engineemg College,Qingdao University of Science and Technology,Qingdao 266061,China;National Engineering and Technology Research Center of Chirality Pharmaceutical,Linyi 273400,China;Shandong Engineering Research Center of Complex Injectables,Linyi 273400,China)

机构地区：[1]青岛科技大学机电工程学院,山东青岛266061 [2]国家手性制药工程技术研究中心,山东临沂273400 [3]山东省复杂注射剂工程技术研究中心,山东临沂273400

出　　处：《中国粉体技术》2021年第1期32-40,共9页China Powder Science and Technology

摘　　要：以乙醇为溶剂、超临界CO2为抗溶剂,通过曲面响应实验设计,分别研究依折麦布质量浓度、结晶釜温度及结晶釜压力对颗粒粒径和分布的影响,对所制备的颗粒进行表征,并优化颗粒工艺参数。实验结果表明:依折麦布颗粒粒径随依折麦布质量浓度的增大而增大,随结晶釜温度的增加先减小后增大,随结晶釜压力的增加而减小;优化后的颗粒制备工艺条件为:依折麦布质量浓度为40 g/L,结晶釜温度为60.46℃,结晶釜压力为13.81 MPa,优化后依折麦布颗粒平均粒径为10.1μm。Ethyl alcohol was selected as the solvent and supercritical carbon dioxide(SC-CO2)was used as the antisolvent.The Box-Behnken design-response surface method(BBD-RSM)was applied to investigate and optimize the effects of mass concentration of Ezetimibe,crystallizer temperature and crystallizer pressure on the size and the distribution of Ezetimibe particles systematically.The particles were characterized by SEM and Malvern laser particle size analyzer.And the process parameters of the particle preparation was optimized.It is found that the particle size of Ezetimibe increases with the increase of mass concentration of Ezetimibe,decreases firstly and then increases with the increase of crystallizer temperature,and decreases with the increase of crystallizer pressure.The optimum conditions are obtained mass concentration of Ezetimibe 40 g/L,crystallizer temperature 60.46℃and crystallizer temperature 13.81 MPa.The optimal average particle size of Ezetimibe is 10.1μm.

关 键 词：超临界CO2抗溶剂法 依折麦布颗粒 曲面响应法 工艺参数 

分 类 号：R972[医药卫生—药品]