伪三元相图联合星点设计效应面法优化复方苦参碱微乳凝胶处方

Optimization of Prescription of Compound Matrine Microemulsion Gel by Pseudo Ternary Phase Diagram Combined with Central Composite Design Response Surface Methodology

采用伪三元相图联合星点设计效应面法(CCD-RSM)获得制备复方苦参碱微乳凝胶的最佳处方。方法:筛选凝胶基质在不同水量中的溶解度,初步评价固体微乳的成乳能力,采用伪三元相图获得形成微乳的区域。分别以凝胶基质卡波姆质量百分比(X1)、混合表面活性剂质量百分比(X2)、水的含量(X3)为考察对象,以外观等级(Y1)、苦参碱载药量(Y2)、辣椒碱载药量(Y3)为微乳凝胶的评价指标,根据CCD-RSM计算获得复方苦参碱微乳凝胶最佳处方,并对其进行验证。结果:尼泊金乙酯、聚乙二醇单月桂酸酯、卡波姆对复方苦参碱有较好的溶解能力。尼泊金乙酯与聚乙二醇单月桂酸酯质量比为30∶1时微乳区域达到最大。根据CCD-RSM获得最佳处方为苦参碱1 g、辣椒碱0.0286 g、卡波姆0.5 g、混合表面活性剂[m(聚乙二醇单月桂酸酯)∶m(尼泊金乙酯)=30∶1]0.5 g、水9.7 mL。以最佳处方制备的微乳凝胶外观等级为4.8,与预测值偏差4.17%;苦参碱载药量为1.0059,与预测值偏差0.59%;辣椒碱载药量为0.0299,与预测值偏差4.9%。结论:采用伪三元相图联合CCD-RSM优化的复方苦参碱微乳凝胶载药量高,外观性状、均匀度、延展性、p H值均达标,可用于后续研究。

The best formulation of compound matrine microemulsion gel was obtained by pseudo ternary phase diagram combined with central composite design response surface methodology(CCD-RSM).Methods:The solubility of gel matrix in different water volume was screened,and the emulsifying ability of solid microemulsion was preliminarily evaluated.Taking the mass percentage of gel matrix carbomer(X1),the mass percentage of mixed surfactant(X2),and the content of water(X3)as the research objects,and taking the appearance grade(Y1),matrine drug load(Y2),and capsaicin drug load(Y3)as the evaluation indicators of microemulsion gel,the best formula of compound matrine microemulsion gel was obtained according to CCD-RSM calculation,and it was verified.Results:Ethyl paraben,polyethylene glycol monolaurate and carbomer have good solubility for compound matrine.When the ratio of ethyl paraben to polyethylene glycol monolaurate is 30∶1,the microemulsion area reaches the maximum.According to CCD-RSM,the best formula was matrine 1 g,capsaicin 0.0286 g,carbomer 0.5 g,mixed surfactant[m(polyethylene glycol monolaurate):m(ethyl paraben)=30∶1]0.5 g,and water 9.7 mL.The appearance grade of microemulsion gel prepared with the best formulation was 4.8,with a deviation of 4.17%from the predicted value;The drug loading of matrine was 1.0059,with a deviation of 0.59%from the predicted value.The drug loading of capsaicin was 0.0299,with a deviation of 4.9%from the predicted value.Conclusion:The compound matrine microemulsion gel optimized by pseudo ternary phase diagram and CCD-RSM has high drug loading,and its appearance,uniformity,ductility and pH value meet the standards,which can be used for subsequent research.