星点设计-效应面法优化甘草酸磷脂/胆盐混合胶束处方

Optimization of Glycyrrhizin Acid Phospholipids/Bile Salts Mixed Micelles Prescription by Central Composite Design/Response Surface Methodology

摘要:

目的: 制备甘草酸磷脂-胆盐混合胶束,并通过星点设计-效应面法优选其处方。 方法: 采用薄膜分散法制备甘草酸磷脂-胆盐混合胶束,通过单因素试验考察胆盐对磷脂的增溶作用,测定磷脂在胆盐溶液中溶解度。以胆盐摩尔浓度、缓冲盐溶液pH为考察因素,甘草酸溶解度及混合胶束载药量为指标,采用星点设计试验优化处方,并进行多元线性和二项式非线性方程拟合,利用效应面法确定最佳处方配比。 结果: 最佳处方为磷脂-胆盐1.19:1,pH 7.4,胆盐摩尔浓度15 mmol·L^-1,甘草酸溶解度21.12 g·L^-1,混合胶束载药量53.93%,理论预测值与实测值偏差较小,模型具有良好的预测性。 结论: 磷脂-胆盐胶束能显著增加甘草酸的溶解度,优选的处方工艺简便、稳定。

Abstract:

Objective: To prepare glycyrrhizin acid phospholipids-bile salts mixed micelles,and optimize its formulation by central composite design-response surface methodology. Method: Glycyrrhizin acid phospholipids-bile salts mixed micelles was prepared by film dispersion method,solubilization of bile salts to phospholipids was investigated by single factor test,solubility of phospholipids in bile salt solution was determined.The molar concentration of bile salts and pH of buffered saline solution were selected as investigation factors,with solubility of glycyrrhizin acid and drug loading of mixed micelles as indexes,formulation was optimized by central composite design test,and fitted by multiple linear and binomial nonlinear equation,then optimum precription ratio was determined by response surface methodology. Result: The best prescription was as following:phospholipids-bile salts 1.19: 1,pH of buffered saline solution 7.4,the molar concentration of bile salts 15 mmol·L^-1;Solubility of glycyrrhizin acid 21.12 g·L^-1,drug loading of mixed micelles was 53.93%;There was a little deviation between the theoretic value and the measured value,it showed that this model had a good prediction. Conclusion: The solubility of glycyrrhizin acid could significantly increase by preparing bile salts-phospholipids micelles,and this optimized technology was simple and stable.