超临界CO₂抗溶剂法制备依折麦布颗粒

Preparation of Ezetimibe by supercritical CO₂anti-solvent process

张 卓^1,2,3,李庆领¹,郝贵周^2,3,曹荣凯^2,3,郝明洁¹,胡德栋^1,2,3

（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）

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。

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。

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

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

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