中心组合设计法优化3′,5′-二辛酰基氟苷药质体制备工艺  

OPTIMIZATION OF THE PREPARATION OF 3′,5′-DIOCTANOYL-5-FLUORO-2′-DEOXYURIDINE PHARMACOSOMES USING CENTRAL COMPOSITE DESIGN

作　　者：张志荣[1] 王建新[2] 吕剑[1] 

机构地区：[1]四川大学药学院,四川成都610041 [2]上海市中药研究所,上海200127

出　　处：《药学学报》2001年第6期456-461,共6页Acta Pharmaceutica Sinica

基　　金：国家杰出青年科学基金 ( 3992 5 0 39);国家自然科学基金( 39970 877);高等学校博士学科点专项科研基金;高等学校骨干教师资助计划项目

摘　　要：目的　采用中心组合设计法优化 3′,5′ 二辛酰基 5 氟脲嘧啶脱氧核苷药质体的制备工艺。方法　以薄膜 超声分散法制备药质体 ,以平均粒径、包封率、载药量和综合指标为因变量 ,对药物与磷脂的比例、F 68浓度和三硬脂酸甘油酯浓度 3个自变量的各个水平进行二项式拟合 ,效应面法选取较佳工艺条件并进行预测分析。结果　平均粒径、包封率、载药量和综合指标拟合所得多元二次方程的复相关系数分别为 0 93 93 ,0 773 9,0 980 1和 0 83 69。优化条件制备的药质体的平均粒径、包封率和载药量分别为 76nm ,97 4 9%和 2 9 3 7%。结论　中心组合设计有应用简便、预测性好等优点 。AIM To optimize the preparation of 3′,5′ dioctanoyl 5 fluoro 2′ deoxyuridine pharmacosomes (DO FUdR PS) by using central composite design. METHODS DO FUdR PS was prepared by a thin layer ultrasonication technique. The effects of drug phosphatidycholine ratio, pluronic F 68 concentration (%, w/v) and glycerol tristearate (%, w/v) concentration on the mean particle size, entrapment ratio (ER) and drug loading (DL) were investigated. A second order polynomial equation was fitted to the data and the resulting model was used to predict the response in the optimal region. RESULTS All the investigated response variables were found to be highly dependent on the formulation variables. Under the optimized conditions, the mean particle size, ER and DL of DO FUdR PS were 76 nm, 97 49% and 31 44%, respectively, which highly agreed with the predicted values. CONCLUSION Central composite design was successfully used to optimize the preparation of DO FUdR PS.

关 键 词：3′ 5′-二辛酰基-5-氟脲嘧啶脱氧核苷 药质体 中心组合设计 

分 类 号：TQ460.6[化学工程—制药化工]