Box-Behnken响应面法优化穿心莲内酯自微乳的制备工艺

Optimization of the Preparation Technology of Andrographolide Self-microemulsion by Box-Behnken Response Surface Methodology

目的:优化穿心莲内酯自微乳的制备工艺。方法:以外观、滴入水相中颜色为指标筛选乳化剂、助乳化剂、油相种类;以伪三元相图筛选各基质的用量范围;以粒径、分散指数、平衡溶解度为考察指标,以综合评分为响应值,以乳化剂质量分数、助乳化剂质量分数、油相质量分数为响应因子,采用Box-Behnken响应面法优化穿心莲内酯自微乳的制备工艺。结果:优化的穿心莲内酯自微乳制备工艺以聚氧乙烯氢化蓖麻油为乳化剂,二乙二醇单乙基醚为助乳化剂,油酸聚乙二醇甘油酯为油相,三者质量比为40∶59∶10。在此工艺条件下制得的自微乳粒径为(38.15±1.56)nm、分散指数为0.12±0.01、平衡溶解度为(5.97±0.02)mg/mL,与预测值(39.72 nm、0.11、6.04 mg/mL)的相对误差分别为3.95%、3.54%、1.16%,实测值与预测值一致性良好。结论:优化所得穿心莲内酯自微乳制备工艺稳定、可行,适用于该制剂的制备。

OBJECTIVE:To optimize the preparation technology of Andrographolide self-microemulsion.METHODS:The types of emulsifier,co-emulsifer and oilphase were screened with appearance,color of them in water phase as indexes.The amount range of each matrix was screened by using pseudo-ternary phase diagram.The preparation technology of Andrographolide self-microemulsion was optimized by Box-Behnken response surface technology with particle size,dispersion index and equilibrium solubility as evaluation indexes,comprehensive score as response value,using mass fraction of emulsifier,mass fraction of co-emulsifier and mass fraction of oil phase as response factors.RESULTS:The optimal preparation technology of Andrographolide self-microemulsion included that polyoxyethylene hydrogen sesame oil as emulsifier,diethylene glycol mono ethyl ether as emulsifier,oleic acid polyethylene glycol glyceride as oil phase,with weight ratio of 40∶59∶10.Under the condition,particle size of obtained self-microemulsion was(38.15±1.56)nm,dispersion index was 0.12±0.01 and equilibrium solubility was(5.97±0.02)mg/mL,relative error of which to predicted value(39.72 nm,0.11,6.04 mg/mL)were 3.95%,3.54%,1.16%.The measured value was in good agreement with the predicted value.CONCLUSIONS:The optimal Andrographolide selfmicroemulsion is stable,feasible and suitable for the preparation of the self-microemulsion.