多西他赛冻干脂质体复溶后粒径分布影响因素考察研究  

Influence on the Distribution of Rehydrated Particle Sizes of Freeze-Dried Docetaxel Liposome

作　　者：张国喜[1,2] 刘汉清[1] 叶强[2] 程昕伟[1] 

机构地区：[1]南京中医药大学,南京210046 [2]南京绿叶思科药业有限公司,南京210061

出　　处：《中国药学杂志》2012年第12期976-978,共3页Chinese Pharmaceutical Journal

摘　　要：目的考察多西他赛冻干脂质体复溶后粒径分布的影响因素,为制备满足临床运用的产品提供依据。方法采用单因素法,分别以不同种类的负电荷磷脂、不同磷酯酰胆碱(PC)含量的卵磷脂、不同种类与浓度的冻干保护剂及不同冻干工艺制备多西他赛冻干脂质体,考察各因素对其冻干复溶后粒径的影响。结果最佳膜材组成为二棕榈酰磷脂酸(DPPA)、PC含量92%的卵磷脂,最佳冻干保护剂为20%的海藻糖;最佳冻干工艺为速冻、升华干燥时间19 h、解析干燥时间9 h。结论负电荷磷脂、冻干保护剂、卵磷脂的PC含量及冻干工艺对多西他赛冻干脂质体复溶后的粒径均有影响。OBJECTIVE To investigate factors that affected the distribution of rehydrated particle size of freeze-dried docetaxel liposome and develop a technique of producing docetaxel liposome that can meet clinical requirements. METHODS The single factor method was utilized in this study. Docetaxel liposome were prepared using different types of negatively charged phospholipids, or leci- thins with varying phosphatidylcholine （PC） content, or various cryoprotectants at different gradient concentrations, followed by freeze- drying with different protocols. The particle sizes of corresponding rehydrated products were compared and the effects of different factors were analyzed. RESULTS The optimal liposomal membrane was composed of dipalmitoyl phosphatidic acid（ DPPA）, 20% trehalose and lecithin containing 92% PC. The best freeze-drying protocol included following steps： flash freezing, 19 h of sublimation-drying and 9 h of desorption-drying. CONCLUSION The parameters, including negatively charged phospholipids, eryoprotectants, PC con- tent of lecithin and lyophilization protocols, had various effects on the particle sizes of reconstituted docetaxel liposome,

关 键 词：多西他赛 冻干脂质体 粒径 二棕榈酰磷脂酸 磷酯酰胆碱 卵磷脂 海藻糖 

分 类 号：R944[医药卫生—药剂学]