中心组合设计法优化3′,5′-二辛酰基-氟苷药质体制备工艺

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0.9393,0.7739,0.9801和0.8369.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,97.49%和29.37%.结论中心组合设计有应用简便、预测性好等优点,制备的药质体符合设计要求.

Optimization of the preparation of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine pharmacosomes using central composite design]

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.