丹皮酚前非离子体的制备及其体外透皮渗透试验

Optimization of Preparation Technology for Paeonol Proniosomes by Central Composite Design-Response Surface Methodology and Investigation of Its in vitro Percutaneous Permeability

摘要:

目的：优选丹皮酚前非离子体的制备工艺并考察其体外透皮性能。方法：选取胆固醇、大豆卵磷脂和山梨醇脂肪酸酯-60（span-60）的质量为自变量，平均粒径和包封率为因变量，对自变量各水平进行二项式拟合，通过效应面法优选丹皮酚前非离子体处方并进行预测分析。采用Franz扩散池试验，以离体裸鼠皮肤为透过膜，生理盐水为接收液，采用HPLC测定丹皮酚含量，比较丹皮酚前非离子体、丹皮酚前非离子体软膏及丹皮酚普通软膏单位面积累积经皮渗透量（Q）及稳态渗透速率（J_s）。结果：最佳处方为胆固醇7.53 mg，大豆卵磷脂107.86 mg，Span-60 74.49 mg，丹皮酚5 mg；丹皮酚前非离子体包封率64.16%，平均粒径11.15 μm，二项式模型拟合良好。丹皮酚前非离子体软膏、普通软膏、前非离子体的Q12 h分别为（96.20±5.87），（75.83±18.42），（125.54±8.87）μg·cm^-2，J_s分别为7.826，5.967，10.327 μg·cm^-2·h^-1。结论：星点设计-效应面法能准确反映多因素多水平交互影响，适用于制剂处方工艺的优化。丹皮酚前非离子体及其软膏的经皮渗透能力高于丹皮酚普通软膏。

Abstract:

Objective: To optimize formulation of paeonol proniosomes and investigate its transdermal performance. Method: Taking quality of cholesterol,soybean lecithin and span-60 as independent variables,average particle size and entrapment efficiency as dependent variable,various levels of independent variables were fitted by binomial equation,response surface methodology was used to optimize formulation,prediction was carried out through comparing the observed and predicted value.Franz diffusion cell test was adopted by taking physiological saline as acceptable liquid and nude mouse skin as membrane,HPLC was adopted to determine the content of paeonol,steady state permeation rate(J_s) and unit area cumulative percutaneous penetration amount(Q) of paeonol proniosomes,paeonol proniosomes oinements and ordinary ointments were compared. Result: Optimum formulation was as follows:cholesterol 7.53 mg,soybean lecithin 107.86 mg,span-60 74.49 mg, peaonol 5 mg;Encapsulation efficiency of these prepared paeonol proniosomes was 64.16%,average particle size was 11.15 μm,binomial model fitting was good.Q12 of paeonol proniosomes,paeonol proniosomes ointments and ordinary ointments were (125.54±8.87),(96.20±5.87),(75.83±18.42) μg·cm^-2,J_s were 10.327, 7.826,5.967 μg·cm^-2·h^-1,respectively. Conclusion: Central composite design-response surface methodology could accurately reflect interaction of multiple factors and levels,which was suitable for optimizing formulation.Penetration capacity of paeonol proniosomes and paeonol proniosomes ointments were higher than ordinary ointments.