超临界CO_2抗溶剂法制备左旋聚乳酸微粒的工艺研究  

Preparation of PLLA Microparticles by Supercritical CO_2 Anti-solvent Technology

作　　者：颜庭轩[1] 王志祥[1] 黄德春[1] 黄娟[1] 孙思杭[1] 党蓓蕾[1] 

机构地区：[1]中国药科大学制药工程教研室,江苏南京210009

出　　处：《今日药学》2013年第1期4-7,共4页Pharmacy Today

基　　金：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)

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8μm)、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.

关 键 词：超临界抗溶剂法 PLLA 玻璃化温度 药物载体 过饱和度 

分 类 号：R943[医药卫生—药剂学]