麝香舒活灵水凝胶剂的制备与体外评价

Preparation and in vitro evaluation of Shexiang Shuhuoling Hydrogel

目的 通过基于水凝胶的剂型改良,制备麝香舒活灵水凝胶剂(Shexiang Shuohuoling Hydrogel,SS-H),解决原麝香舒活灵酊剂(Shexiang Shuhuoling Tincture,SS-T)的刺激性和亲水性活性成分递送不良等问题,并优化SS-H处方。方法通过单因素试验筛选SS-H制备的最佳条件,并考察凝胶流变特性、平衡含水量与氧气渗透性等物化表征。在胶原酶模拟体表环境下考察体外生物降解,并比较SS-H与粗提物和SS-T的体外释放,皮肤渗透性能和生物相容性。结果 SS-H的最佳处方为2%卡波姆、5%甘油、1.6%三乙醇胺,不需要促透剂。SS-H具有可观的可涂抹性和物理强度,并表现出一定的保湿性与透氧性,体外降解性能良好。在亲脂性药物的体外释放和皮肤渗透率未受显著影响下,亲水性药物羟基红花黄色素A在SS-H中的累积释放率和皮肤渗透率比在SS-T中分别提高了20%和40%。此外SS-H将皮肤细胞活力相对粗提物提高了20%~60%,显示出良好的生物相容性,而SS-T对细胞活力无明显促进作用。结论 对SS-T进行凝胶制剂的改良,是有效的剂型改良策略,制备的SS-H物化性能良好,可缓解原酊剂对人体的刺激性并增强亲水性活性成分的局部递送效果,为优化基于中药复方的传统外用制剂提供了新的剂型改良策略。

Obiective To Solve the problems of irritation of original Shexiang Shuhuoling Tincture(SS-T)and poor delivery of hydrophilic active ingredients by improving its formulation based on hydrogels.Methods The optimum preparation conditions of hydrogels were selected by single factor experiment,and the rheological properties,equilibrium water content and oxygen permeability of hydrogels were investigated.In vitro biodegradation was investigated in a simulated body surface environment with collagenase,and in vitro release,skin permeability and biocompatibility of the gel were compared with crude extracts and original tinctures.Results The optimal prescription of Shexiang Shuohuoling Hydrogel(麝香舒活灵水凝胶剂,SS-H)was 2%carbomer,5%glycerol,1.6%triethanolamine,and no penetration enhancer was required.SS-H had considerable smear ability and physical strength,and also showed certain moisture retention,oxygen permeability,and good degradation performance in vitro.While the in vitro release and skin permeability of lipophilic drugs were not significantly affected,the cumulative release and skin permeability of hydrophilic drug hydroxysafflor yellow A in SS-H were increased by 20%and 40%compared with those in SHL-T,respectively.In addition,SS-H increased the viability of skin cells by 20%—60%compared with crude extract,showing good biocompatibility,while SS-T had no obvious promoting effect on cell viability.Conclusion The improvement of the gel preparation of SS-T is an effective formulation improvement strategy.The prepared SS-H has good physical and chemical properties,which can alleviate the irritation of the original tincture to human body and enhance the local delivery effect of hydrophilic active ingredients.This study provides a new formulation improvement strategy for optimizing the traditional topical preparation based on traditional Chinese medicine compound.