星点设计效应面法优化胰岛素油溶液的处方

Application of central composite design-response surface methodology to the preparation of insulin oil solution

目的采用中心复合设计法优化胰岛素-胆盐与磷脂冻干复合物处方,以获得稳定的胰岛素油溶液。方法分别考察了叔丁醇用量和胆盐与磷脂质量比对冻干复合物的载药量和溶解时所需油相质量等指标的影响。用线性方程和二次多项式描述各指标及总评"归一值"与两个因素之间的数学关系,根据总评"归一值"的最佳数学模型描绘效应面,选择最佳处方,并进行预测分析。结果两个因素和两个评价指标及总评"归一值"之间存在定量关系。优选的最佳处方为叔丁醇0.475 g,胆盐与磷脂质量比2.810。优化处方各指标的预测值和目标值接近。结论所建立的模型预测性良好,可用于优化胰岛素-胆盐与磷脂冻干复合物处方,并获得稳定的胰岛素油溶液。

Objective To obtain a stable oil solution loaded insulin, the formulations of bile salt/SPC freeze- dried complex were prepar.ed and optimized using central composite design-response surface methodology. Methods The effect of formulation variables（ amount of ten-butyl alcohol, and ratio of bile salt/SPC） on a number of response variables was systemically investigated. The response variables were^amount of solubiliz- ing insulin in freeze-dried complex and amount of soybean oil used to dissolve freeze-dried complex. A de- sirability function that combines these two response variables was constructed. A second-order polynomial eqution was. fitted to the data, and the resulting eqution was used to perdict the responses in the optimal re- gion. Results All the investigated response variables were found to be highly dependent on the formulation variables. It was found that optimum overall desirability of the insulin freeze-dried complex could be ob- tained at 0. 475 g of ten-butyl alcohol, and at 2. 810 of ratio of bile salt/SPC. The experimental values of the response variables highly agreed with the predict values. Conclusions Central composite design-response sur- face methodology is successfully used to optimize the preparation of insulin-loaded bile salt/SPC freeze- dried complex, in order to obtain the stable insulin oil solution. Overall desirability can be used to represent the most desirable variables in experimental design.