活血止痛凝胶贴膏与微乳凝胶剂的体内外渗透性比较研究

Comparative study on in vivo and in vitro permeability of Huoxue Zhitong gel patch and microemulsion gel

建立透皮接收液以及体内透析液中丹皮酚(paeonol, Pae)、丁香酚(eugenol, Eug)及胡椒碱(piperine, Pip)的含量测定方法,并对活血止痛凝胶贴膏与微乳凝胶剂的体外渗透性和体内药动学进行研究。采用Franz扩散池法考察活血止痛凝胶贴膏与微乳凝胶剂的经皮渗透性比较研究;采用微透析技术对其进行体内药动学比较研究。分别利用HPLC及UPLC-MS测定透皮接收液及体内透析液中Pae、Eug及Pip的含量;经皮渗透性结果表明,凝胶贴膏中3个成分的累积透过量(Q_(n))和透皮速率(J_(ss))均为Eug>Pae>Pip;微乳凝胶剂中除了Pip未达到定量检测限之外,其他2种成分的Q_(24)和J_(ss)的变化规律与凝胶剂是一致的。两者比较发现,凝胶贴膏中Pae、Eug及Pip的Q_(n)和J_(ss)明显高于微乳凝胶剂,说明凝胶贴膏中药物释放速度更快。从药动学结果来看,凝胶贴膏经皮给予后,3个成分可迅速透过皮肤,且驻留时间较长;经皮给予微乳凝胶剂后,Pae和Eug可迅速透过皮肤,但去除药物后,2种成分在体内的浓度逐渐下降。两者比较发现,凝胶贴膏中Pae、Eug及Pip的C_(max)、AUC_(0-760)、MRT均高于微乳凝胶剂,说明凝胶贴膏更能促进药物的渗透,还能增加药物的皮肤滞留时间。通过上述研究,为活血止痛膏剂型改进提供了参考。

This study aims to establish a method for determination of paeonol(Pae), eugenol(Eug), and piperine(Pip) content in receptor liquid and research on the permeability and pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The Franz diffusion experiment was conducted to assess the percutaneous permeability, and the microdialysis method was employed to assess pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The content of Pae, Eug, and Pip in receptor liquid in vitro and in vivo was determined by HPLC and UPLC-MS. The Q_(n) and J_(ss) of Pae, Eug, and Pip in the gel patch were significantly higher than those in the microemulsion gel, indicating that the drug release was faster in the gel patch. The C_(max), AUC_(0-760), and MRT of Pae, Eug, and Pip in the gel patch were higher than those in the microemulsion gel, indicating that the gel patch can promote the penetration and prolong the skin residence of the drug. The results of this study provide reference for improving the dosage form of Huoxue Zhitong patch.