ZHANG Zhuo^1,2,3,LI Qingling¹,HAO Guizhou^2,3,CAO Rongkai^2,3,HAO Mingjie¹,HU Dedong^1,2,3

(1.Electromechanical Engineerng College,Qingdao University of Science and Technology,Qingdao 266061,China;2.National Engineering and Technology Research Center of Chirality Pharmaceutical,Linyi 273400,China;3.Shandong Engineering Research Center of Complex Injectables,Linyi 273400,China)

Abstract：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 10.1 μm.

Keywords：supercritical CO2 anti-solvent process; Ezetimibe particles; response surface method; process parameters

中图分类号：R972

文献标志码：A

文章编号：1008-5548(2021)01-0032-09

DOI：10.13732/j.issn.1008-5548.2021.01.004

收稿日期：2020-07-02，修回日期：2020-09-28，在线出版时间：2020-11-02 14:16。

第一作者简介：张卓(1991—),女,博士研究生,研究方向为超临界CO2纳微颗粒制备技术研究。E-mail:zhangzhuoqust@163.com。

通信作者简介：胡德栋(1970—),男,博士,副教授,研究方向为超临界流体技术。E-mail:hudedong@126.com。