星点设计-效应面法优化普仑司特自微乳给药系统

Optimization of self-microemulsion drug delivery system of pranlukast hydrate using central composite design-response surface methodology

目的:采用星点设计-效应面法优化普仑司特自微乳给药系统(self-microemulsions drug delivery system,SMEDDS)处方。方法:通过溶解度实验和伪三元相图筛选普仑司特SMEDDS处方组成,采用星点设计-效应面法,以微乳粒径、Zeta电位和药物在体系中的平衡溶解度为效应值,优化处方中油相用量(w/w)、无水乙醇用量(w/w)、聚氧乙烯蓖麻油(Cremophor EL)与三乙醇胺(triethanolamine,TEA)的比值K,并进行处方验证。结果:优化后的处方为油酸乙酯22.1%、无水乙醇18.0%、Cremophor EL与TEA的比值K为2.0,普仑司特SMEDDS粒径为(70.8±2.4)nm,电位为(-24.97±1.34)m V,药物在体系中的溶解度为(41.1±0.8)mg·g^(-1),实测值与预测值接近。结论:星点设计-效应面法适用于普仑司特自微乳给药系统的处方优化,所建立的数学模型预测性能良好。

Objective： To optimize the formulation of pranlukast hydrate self-microemulsions drug delivery system（ SMEDDS） using central composite design-response surface methodology. Methods： Components of pranlukast hydrate SMEDDS were screened by solubility testing and pseudo-ternary phase diagram. The optimal prescription was determined using the central composite design-response surface methodology. Particle size,zetapotential and solubility were taken as dependent variables,and the percentage of oil phase in formulation（ w / w）,the usage amount of anhydrous ethanol in formulation（ w/w） and the ratio of cremophor EL to TEA（ K） as independent variables. Results： Optimized formulations were 22. 1% ethyl oleate,18.0% anhydrous ethanol,and the cremophor EL/TEA ratio K was 2. 0. The mean particle size,zeta-potential and solubility of pranlukast hydrate was（ 70.8 ± 2.4） nm,（- 24.97 ± 1.34） m V,and（ 41.1 ± 0.8） mg·g^（-1）,respectively. The observed values were close to predicted values. Conclusion： The central composite design-response surface methodology is useful for the formula optimization of pranlukast hydrate SMEDDS. The prediction accuracy of the established model is good.