基于药物-皮肤的相互作用探究盐酸特比萘芬体外透皮特性

目的 考察盐酸特比萘芬的体外透皮特性，探究盐酸特比萘芬与皮肤的相互作用，基于药物-皮肤相互作用阐明盐酸特比萘芬透皮特性的机制。方法 比较盐酸特比萘芬经皮渗透及其皮内滞留以及在皮肤各层的分布；利用衰减全反射红外光谱、差示扫描量热、拉曼光谱研究药物与皮肤的相互作用，并对药物与角质层角蛋白及脂质的相互作用进行计算机模拟和计算。结果 盐酸特比萘芬经皮渗透后高滞留低渗透，滞留的药物多分布于角质层。盐酸特比萘芬与角质层中脂质和角蛋白均有相互作用，该作用使药物自身难于透过皮肤，并导致较大的透过变异性。结论 盐酸特比萘芬与皮肤脂质和角蛋白的相互作用是其表现出典型的皮肤低渗透、高滞留特性的机制之一。本研究为盐酸特比萘芬体外透皮高滞留、低渗透特性提供理论依据。

Research on Transdermal Properties of Terbinafine Hydrochloride in Vitro Based on Drug-skin Interactions

OBJECTIVE To investigate the transdermal properties of terbinafine hydrochloride in vitro, explore the interactions between terbinafine hydrochloride and skin, and clarify the mechanism of the transdermal properties of terbinafine hydrochloride based on drug-skin interactions. METHODS Drug transdermal penetration, intradermal retention, and distribution in various layers of the skin had been compared. Drug-skin interactions had been studied with ATR-FTIR, DSC and Raman spectra, and the interactions between keratin, lipids of stratum corneum(SC) and drug were simulated and calculated in the computer. RESULTS Terbinafine hydrochloride exhibited high skin retention and low penetration. The retained drugs were mostly distributed in the SC. It could interact with both the lipids and keratin in the SC. These interactions made transdermal process difficult and caused great penetration variation. CONCLUSION The interaction of terbinafine hydrochloride with skin lipids and proteins is one of the mechanisms by which it exhibits typical high skin retention skin and low permeability. It provides a theoretical basis for the transdermal properties of high retention and low permeability of terbinafine hydrochloride in vitro.