星点设计-效应面法优化硫氰酸红霉素肺靶向明胶微球的配方

用星点设计-效应面法优化硫氰酸红霉素明胶微球的处方,以期得到分散性好、粒径符合要求的明胶微球。本研究采用乳化-化学交联法制备,以明胶浓度、油水比例、乳化剂浓度为自变量,微球的平均粒径、载药量、包封率、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。根据因变量效应面法选取较佳工艺,并在此基础上制备了硫氰酸红霉素微球,且进行了优化处方的验证。结果显示,二项式模型拟合效果较多元线性回归要好,最佳优化处方为明胶浓度0.156g/mL、油水比例12∶2、乳化剂浓度0.03g/mL,根据优化工艺制备的微球分散性好,平均粒径、载药量、跨距、包封率分别为12.51μm、21.28%、1.51和84.39%。体外释药特性研究表明,该微球符合一级方程规律,具有明显的缓释效果。通过星点设计-效应面法成功建立了处方优化模型,且预测性良好。

Optimization of Preparation Formulation of Lung Targeting Gelatin Microspheres of Erythromycin Thiocyanate by Central Composite Design-response Surface Methodology

Gelatin microspheres of preparation formulation were optimized by central composite design to anticipate gain gelatin microspheres of good dispersion and particle size to meet the requirements.Targeting microspheres were prepared by emulsion chemical-cross linking method,the effect of independent variables(concentration of gelatin,volume percent of water phase and organic phase and emulsifier concentration)were evaluated with a number of response variables.Response variables were mean diameter,drug content,encapsulation efficiency,diameter span.Second-order polynomial and multiple linear regressions were fitted to the data.According to the response surface methodology,the best formulation was selected.The results showed that second-order polynomial fitting was much better than multiple linear regression,the optimal conditions were gelatin concentration 0.156 g/mL,volume percent of water phase and organic phase 12∶2,emulsifier concentration 0.03 g/mL.According to the optimal conditions,the mean diameter,drug content,encapsulation efficiency,diameter span were 12.51μm,21.28%,1.51 and 84.39%.The research of release of the drug in vitro indicated that the release profiles followed first-order equation,it showed that the microspheres had obviously sustained-release effect.The reliable model was established using response surface methodology and the optimum mathematic model is highly predictive.