冻干工艺及保护剂对羟基喜树碱脂质体质量的影响

用薄膜水化-高压均质法制备羟基喜树碱脂质体,以葡聚糖凝胶色谱法分离脂质体和游离药物,采用HPLC法测定包封率。通过差示扫描量热法测定含不同保护剂的脂质体的最低共熔点和玻璃化转变温度,并比较冻干品外观、冻干前后脂质体包封率和粒径的变化,优选出最佳的冻干工艺、冻干保护剂种类及比例。结果表明,以6%蔗糖为冻干保护剂,经4℃、1 h,-18℃、12 h和-35℃、5 h逐步预冻,然后于-54℃冷冻干燥24 h,制得的冻干品外观良好,脂质体复溶后粒径变化小,包封率达(87.0±2.7)%。

Effects of Lyophilization Process and Lyoprotectants on the Quality of Hydroxycamptothecine Liposomes

The liposomes loaded with 10-hydroxycamptothecine were prepared by thin film hydration and high pressure homogenize method.The liposomes and free drug were separated by Sephadex G-75,the encapsulation efficiency was determined by HPLC.The eutectic points and glass transition temperatures of liposomes containing different lyoprotectants were determined by differential scanning calorimeter.The appearance,encapsulation efficiency and particle size before and after lyophilization of the products were compared to optimize the process and lyoprotectants.The results showed that 6% sucrose was the suitable lyoprotectant,and the lyophilization process moved from prefreezing condition of 4 ℃ for 1 h,-18 ℃ for 12 h and-35 ℃ for 5 h,then lyophilized at-54 ℃ for 24 h.The lyophilized product was of good appearance,the encapsulation efficiency was(87.0±2.7)%.The particle size varied little before and after lyophilization.