中心组合设计法优化雌二醇PEG-PLA微球制备工艺研究

Optimization of Preparation of Estradiol-loaded PEG-PLA Microspheres by Central Composition Design

利用中心组合设计法优化雌二醇聚乙二醇-聚乳酸微球制备工艺,提高微球制备质量,并对其特性进行预测。采用油/水乳剂溶剂挥发法制备微球。自变量为水相聚乙烯醇浓度、有机相聚乙二醇-聚乳酸浓度和理论载药量,以微球产率、包封率、平均粒径和跨距为因变量,对各自变量的各水平进行多元线性回归和二项式拟合,根据因变量面法选择较佳工艺条件并对优化区间进行预测。结果表明,产率、包封率、平均粒径和跨距用二项式模型拟合较好,复相关系数R分别为0.912 6、0.964 2、0.963 2和0.962 8,包封率、平均粒径和跨距的预测值与实测值的偏差分别为2.84%、7.56%和8.58%。中心组合设计法优化处方和制备工艺,方法简便,可对多因素和多指标的实验进行综合优化筛选,对试验结果预测较准确,是进行处方和制备工艺优化筛选的较佳方法。

The usage of central composite design to optimize the preparation of estradiol-loaded PEG-PLA microspheres,and its potential use in predictable preparation were investigated.Microspheres were prepared by O/W emulsion solvent evaporation method.Effects of three independent variables i.e.,polyvinyl alcohol concentration in aqueous phase（%,w/v）,PEG-PLA concentration in organic phase（mg/ml）and theoretical drug content（%,w/w）,were investigated on four response variables.Response variables selected in the research were yield,loading efficiency,mean diameter and span of dispersity.Second-order polynomial and linear equations were fitted to the data,and the resulting equations were used to produce three dimensional response surface graphs.So we could select the optimal experimental conditions.Four response variables were found to be dependent on three independent variables by second-order polynomial equations.Relevence cofficients of yield,loading efficiency,mean diameter and span of dispersity were 0.912 6,0.964 2,0.963 2 and 0.962 8 respectively.According to optimal experimental conditions,an optimized formulation were prepared and evaluated for loading efficiency,mean diameter and span of dispersity.The observed values agree well with the resulting equation predicted values.Central composite design can be successfully used to optimize the preparation of PEG-PLA microspheres loaded with estradiol,and has potential in many areas.