Box-Behnken试验设计法优化宝泻灵凝胶膏剂处方及其体外透皮特性研究

Optimization for prescription of Baoxieling Hydrogel Patch using Box-Behnken test design and research on its transdermal permeability in vitro

目的运用Box-Behnken试验设计法优化宝泻灵凝胶膏剂的处方并研究其体外透皮吸收行为。方法以凝胶膏剂初黏力、均匀性、涂展性、稠度、皮肤追随性、反复揭贴性与残留等多个指标的综合评分为响应值,采用Box-Behnken试验设计法,对聚丙烯酸钠NP 800、甘羟铝、填充剂的用量进行优化,确定最佳处方组合并进行验证试验;采用改良的Franz扩散池,通过体外透皮试验,用HPLC法同时测定最佳处方中桂皮醛、丁香酚、吴茱萸碱和吴茱萸次碱的体外透皮渗透量。结果优选出宝泻灵凝胶膏剂最佳配方为聚丙烯酸钠NP 800-甘羟铝-填充剂(0.82∶0.02∶1.56),填充剂和交联剂甘羟铝的用量是最主要影响因素,体外透皮行为符合零级动力学过程。结论优选的宝泻灵凝胶膏剂膏体均匀,稠度适宜,易涂布,黏着性及透皮效果好,可为宝泻灵的新制剂开发提供基础。

Objective To optimize the prescription of Baoxieling Hydrogel Patch （BHP） using Box-Behnken test design and to investigate its transdermal absorption properties in vitro. Methods Taking the comprehensive scores of the early adhesion, uniformity, ductility, consistence, skin adhesive ability, repeated exposing paste, and residue as response values, Box-Behnken test design was used to optimize the amounts of sodium polyacrylate NP 800, aluminum glycinate, and fillers, and to validate the optimal formulation. The percutaneous permeation of cinnamaldehyde, eugenol, evodiamine, and rutaecarpine in the optimal formulation was studied by in vitro transdermal delivery experiment with Franz diffusion cells and their contents were determined by HPLC. Results The optimal ratio of the prescription was as follows： sodium polyacrylate NP 800-aluminum glycinate-fillers （0.82 ： 0.02 ：1.56）. The foremost factors were fillers and aluminum glycinate. Its transdermal absorption met zero order dynamic process. Conclusion The optimal prescription has uniform paste, suitable consistence, easy ductility, moderate adhesion, and perfect transdermal effect. It could provide the foundation for the development of new prescription of Baoxieling.