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[摘要]
目的 星点设计-效应面法优化阿德福韦包合物的制备工艺.方法 以饱和水溶液法制备阿德福韦-β-环糊精包合物,采用星点设计优化制备工艺,以β-环糊精与阿德福韦的投料配比、包合时间、包合温度为自变量,包合率、收率为因变量,分别进行多元线性回归和二项式方程拟合,依据最佳数学模型描绘效应面选择最佳处方工艺进行验证试验.结果 二项式方程拟合度较高,预测性好,相关系数r=0.965;效应面法优选出的最佳工艺为:β-环糊精与阿德福韦的投料配比约为3:1,包合时间为5 h,包合温度为60 ℃.最佳工艺验证试验结果与二项式拟合方程预测值偏差为(1.31±0.69)%.结论 应用星点设计-效应面优化法能够精确有效地优化阿德福韦-β-环糊精包合物的制备工艺,优选出的最佳工艺稳定可行,可用于工业生产.
[Key word]
[Abstract]
Objective To optimize the preparation technology of adefovir-β-cyclodextrin inclusion complex by central composite design and response surface methodology. Methods Saturated aqueous solution method was used to prepare adefovir-β-cyclodextrin inclusion complex. The preparation was optimized by central composite design. With β-cyclodextrin/adefovir, inclusion time, and temperature as the independent variables, and with the inclusion rate and yield as the dependent variable, the binomial and linear equations were fitted to the data of overall desirabilities, and the resulting equation was used to produce 3-D response surface graphs, through which optimal formulation was predicted, and the best prescription process was chosen to verity test. Results The fitting of second-order quadratic model was high, and the correlation coefficient was 0.965. The optimum conditions for the preparation of adefovir-β-cyclodextrin inclusion complex were as follows: β-cyclodextrin/adefovir of 3:1, inclusion time of 5 h, and inclusion temperature at 60 ℃. The deviation between the result of best craft verification test and the binomial fitting equation forecast value was (1.31 ± 0.69)%. Conclusion Central composite design and response surface methodology is successfully used to optimize the preparation technology of adefovir-β-cyclodextrin inclusion complex. The optimized process is reliable, stable, and available for the industrial production.
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[基金项目]
国家重点基础研究发展计划(973计划)项目(2010CB735600)