全缘千里光碱脂质体凝胶剂制备工艺的研究  

Study on Preparation of Integerrimine Liposomal Gel

作　　者：郑杭生[1] 张亚军[2] 张彤[1] 徐莲英[1] 

机构地区：[1]上海中医药大学中药学院药剂教研室,上海201203 [2]西北大学,西安710069

出　　处：《中国药学杂志》2009年第7期510-512,513-515,共6页Chinese Pharmaceutical Journal

基　　金：上海市教育委员会科研项目(04cc21);上海市科学技术委员会科研项目(02DZ1912)

摘　　要：目的制备具有高包封率和良好稳定性的全缘千里光碱(INT)脂质体,并将其制成凝胶剂。方法以离心-超滤法测定脂质体的包封率。以包封率为主要指标筛选脂质体制备工艺、主要辅料磷脂与处方中磷脂-胆固醇比例;通过均匀设计法优选制备脂质体的工艺条件;考察药脂比包封率;通过pH梯度主动载药法提高脂质体的包封率;确定脂质体及其凝胶剂的处方工艺,并进行质量与稳定性评价。结果制备INT脂质体的最适方法为薄膜分散法,最适的磷脂为注射级大豆磷脂,处方中磷脂-胆固醇的最佳比例为4∶1;药脂比为1∶10时,薄膜分散法制备INT脂质体的最佳工艺参数为:成膜温度46.3℃,水化液用pH4.0柠檬酸缓冲液(CBS4.0),体积为15.0mL,包封率可达57.45%;药脂比由1∶20增加1∶2,包封率均在60%左右;pH梯度主动载药可显著提高脂质体的药物包封率,主动载药中较合适的水化液为CBS4.0。优选的脂质体包封率为75.21%,平均粒径为284nm,Zeta电位为2.23mV,稳定性实验证明,该脂质体及其凝胶剂稳定性良好。结论薄膜分散法结合pH梯度载药可以制备稳定且高包封率的INT脂质体凝胶剂。OBJECTIVE To prepare integerrimine （ INT ） liposomes with high drug entrapment efficiency （ DEE ） and good stability and then to prepare liposomal gel with INT lipsomes. METHODS The DEE was determined by the method of combined centrifugation and ultrafiltration. Based on the main evaluating index of DEE, the preparation method, type of lecithin, and lecithin-cholesterol ratio were optimized. The processing parameters of the preparation were optimized by uniform design experiment. Drug-lipid ratio DEEs were investigated. And pH gradient active drug loading method was employed to improve the DEE of INT liposome. The optimized liposome and its gel were prepared, and their stability was tested. RESULTS The method of thin film dispersion （ TFD ） was chosen as the preferable method to prepare INT liposome, and the soybean lecithin for injection （PC〉70%） was the optimal lipid, the optimum lecithin-cholesterol ratio was 4 ： 1. When drug-lipid ratio was 1 ： 10, the optimized key processing parameters of TFD were as follows： thin film forming temperature 46.3 ℃, hydration liquid 15.0 mL citric buffer solution （ pH 4.0 ）. The resultant liposomes had a DEE of 57.45%. When drug-lipid ratio increased from 1 ： 20 to 1 ： 2, the DEEs remained at about 60%. The liposomes with high drug-lipid ratio had good physical stability. The method of pH gradient active loading was able to increase the DEE of INT liposomes, and the optimal hydration liquid was citric buffer solution （.pH 4.0）. The optimum formulation of the liposomes for the preparation of gel was designed. The resultant liposome of this formulation had a DEE of 75.21%, a wide size distribution with an average 284 nm and a Zeta potential 2.23 mV. The stability test revealed that the liposome was stable. Then the optimum formulation of liposomal gel was chosen. The stability test showed that the preparation had good stability. CONCLUSION The method of TFD combined with pH gradient active loading can be used to prepare stable and high-DEE

关 键 词：全缘千里光碱 脂质体凝胶剂 均匀设计 pH梯度主动载药 

分 类 号：R944[医药卫生—药剂学]