超临界CO2 抗溶剂法制备左旋聚乳酸微粒的工艺研究-今日药学

超临界CO2 抗溶剂法制备左旋聚乳酸微粒的工艺研究

作者：颜庭轩王志祥黄德春黄娟孙思杭党蓓蕾

单位：中国药科大学制药工程教研室,江苏南京210009

关键词：超临界抗溶剂法 PLLA 玻璃化温度药物载体过饱和度

中图分类号：R943

文献标志码：A

出版年,卷(期):页码：2013,23(1):4-7,

收稿日期：2012 -10 -15

摘要：

目的采用超临界抗溶剂法(SAS)制备可生物降解的左旋聚乳酸(PLLA)超细微粒。方法以二氯甲烷和丙酮为溶剂,CO2 为抗溶剂,制备得到PLLA 微粒,研究各种操作参数对产品质量的影响。结果成功制备得到粒径小(约8 μm)、分布较窄的PLLA 微粒。单因素实验表明:操作压力越高粒径越小;温度大于50 ℃时微粒易团聚;溶液浓度越高,微粒粒径越大;选用一定比例的二氯甲烷-丙酮混合溶剂有助于得到粒径小、分布均匀的微粒。结论正交试验得到优选工艺为:浓度8 mg/ mL,结晶压力16 MPa,温度39 ℃,二氯甲烷:丙酮=2∶1。

Objective To prepared Poly L-lactide acid ( PLLA) by using supercritical CO2 anti-solvent ( SAS) technology. Methods PLLA were prepared by SAS with dichloromethane and acetone as the cosolvent and CO2 as the anti-solvent. The influence of operating parameters on the product quality was studied. Results Microparticle of PLLA were successfully prepared with a narrow particle size(8 μm) approximately. The size of PLLA microparticle decreased along with the operating pressure increasing. There would be agglomerated particles when the operating temperature was above 50 ℃. The particle size increased when the solution concentration increased. The mixture of methylene chloride and acetone mixed solvent would be helpful to obtain narrow particle size distribution for PLLA. Conclusion The orthogonal experiment optimization process conditions are set as follows: PLLA concentrationis 8 mg/ mL, crystallization pressureis 16 MPa, crystallization temperature is 39 ℃, and cosolvent ratio dichloromethane:acetone =2∶1.

基金项目：

江苏省自然科学基金资助项目(编号:BK2012763) 大学生创新药物研制能力提高项目(国家级大学生创新创业训练计划项目)资助项目(编号:J1030830)

作者简介：

颜庭轩,在读研究生,从事制药分离方向的研究

通讯作者：王志祥,教授,博士生导师,从事制药工程领域的教学与科研,Tel:025-83271258,E-mail chinawzx@ sohu. com

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