中心多点等距设计法优化雌二醇聚乳酸羟基乙酸微球的制备工艺  

Optimization of Preparation of Estradiol Polylactic-Co-Glycollic Microspheres by Central Composite Design

作　　者：赵刚[1] 平其能[1] 栾杨[2] 李六文[3] 

机构地区：[1]中国药科大学药剂学教研室,南京210009 [2]山东省医学科学院药物研究所,济南250062 [3]山东师范大学生命科学院,济南250014

出　　处：《中国药科大学学报》2004年第2期122-126,共5页Journal of China Pharmaceutical University

摘　　要：目的 :中心多点等距设计法优化雌二醇聚乳酸羟基乙酸微球制备工艺 ,提高该制剂质量并对其特性进行预测。方法 :微球用油 /水乳剂溶剂挥发法制备 ,自变量为外水相聚乙烯醇浓度、有机相聚乳酸羟基乙酸浓度和理论载药量 ,以微球包封率、产率、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分析。结果 :包封率、产率、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 9796 ,0 90 97,0 9138,0 84 5 5 ,包封率、平均粒径和跨距的预测值与实测值的偏差分别为 - 3 72 % ,6 4 7%和 10 0 6 %。结论 :中心多点等距设计法优化处方和制备工艺 ,对试验结果可较好的进行预测 ,是处方和制备工艺优化筛选的较佳方法。AIM:The usage of central composite design to optimize the preparation of estradiol polylactic co glycollic acid microspheres,and its potential use in predictable preparation were investigated METHOD: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 ),polylactic co glycollic acid 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 loading efficiency,yield,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,by which optimal experimental conditions were selected RESULT:Four response variables were found to be dependent on three independent variables Higher polyvinyl alcohol concentration in aqueous phase,middle polylactic co glycollic concentration in organic phase and middle high theoretical drug content indicated beneficial tendency to increase loading efficiency and to achieve better characteristic According to optimal experimental conditions,an optimized formulation was prepared and evaluated for loading efficiency,mean diameter and span of dispersity The observed values agree well with the resulting equation predicted values CONCLUSION:Central composite design can be successfully used to optimize the preparation of polylactic co glycollic acid microspheres containing estradiol,and it has potential use in many areas

关 键 词：雌二醇 聚乳酸羟基乙酸 微球 中心多点等距设计 制备工艺 

分 类 号：TQ463[化学工程—制药化工]