中心多点等距设计法优化醋酸地塞米松聚丙交酯微球的制备工艺

目的：中心多点等距设计法优化醋酸地塞米松聚丙交酯微球的制备工艺，以提高微球性质的可预测性。方法：微球用溶剂挥发/萃取法制备，自变量为外水相聚乙烯醇浓度、有机相聚丙交酯浓度和投药比，以微球收率、载药量、包封率、平均粒径和跨距为因变量对自变量的各水平进行多元线性回归和二项式拟合，因变量面法选取较佳工艺条件并于较优区进行预测分析。结果：载药量和包封率可用线性模型拟合，复相关系数γ²分别为0.986和0.991；载药量、粒径和跨距可用二项式拟合，复相关系数γ²分别为0.998,0.912和0.935，包封率、平均粒径和跨距的预测值与实测值的偏差分别为-4.09%,-5.18%和-8.33%。结论：中心多点等距设计法优化处方与制备工艺有使用方便，预测性良好的特点，值得推广应用。

OPTIMIZATION OF PREPARATION OF DEXAMETHASONE ACETATE-LOADED POLY(D,L-LACTIDE) MICROSPHERES BY CENTRAL COMPOSITE DESIGN

AIM: Use central composite design to optimize the preparation of dexamethasone acetateloaded poly(d,llactide) microspheres, and evaluate its potential use in predictable preparation. METHODS: Microspheres were prepared by a solvent evaporation/extraction method. Effects of three independent variables, i.e., polyvinyl alcohol concentration in aqueous phase(%, w/v), polylactide concentration in organic phase(%, w/v) and theoretical drug content(%, w/w) were evaluated on a number of response variables. Response variables selected in this study were yield, drug loading, loading efficiency, mean diameter and span of dispersity. Secondorder polynomial and linear equations were fitted to the data, and the resulting equations were used to produce three dimensional response surface graphs, through which optimal experimental conditions were predicted. RESULTS: All response variables were found to be greatly dependent on three independent variables. Lower polyvinyl alcohol concentration in aqueous phase, higher polylactide concentration in organic phase and higher theoretical drug content showed beneficial tendency to increase drug loading and loading efficiency. An optimized formulation was prepared according to optimal experimental conditions and evaluated for loading efficiency , mean diameter and span of dispersity. The observed values agreed well with modelpredicted values. CONCLUSION: Central composite design was successfully used to optimize the preparation of poly(d,llactide) microspheres containing dexamethasone acetate. The method has potential use in other areas.