【摘要】 目的:考察4-萜品醇(TEN)、4-萜品醇庚酸酯(TEN-C7)及肉豆蔻酸异丙酯(IPM)对氟比洛芬(FP)贴剂家兔在体促渗透活性,并对促透剂的促透体内外相关性进行初步探究。方法:以含不同促透剂的FP贴剂进行大耳兔体内药动学实验,计算FP的药动学参数,并使用反卷积分法验证药物的体内外渗透相关性。最后通过体外释放实验以及衰减全反射-傅里叶变换红外光谱法(ATR-FTIR)研究促透剂在药物释放、吸收过程中的作用机制。结果:体内渗透研究表明TEN-C7对FP的透皮递送具有显著的促透作用,并具有良好的体内外相关性(R~2>0.878 3);体外释放实验表明促透剂通过与压敏胶黏合剂分子的相互作用促进药物的释放;ATR-FTIR结果表明不同促透剂对FP的透皮通量增加与角质层脂质迁移率的增加以及促透剂和角质蛋白的相互作用相关。结论:TEN-C7对FP贴剂具有显著促透活性,有必要进一步研究拓宽其应用范围。更多还原

【Abstract】 Objective: To investigate the permeability promoting effects of 4-methyl-1-(1-methylethyl)-3-cyclohexen-1-ol(TEN), 4-methyl-1-(1-methylethyl)-3-cyclohexen-1-yl-heptanoate(TEN-C7) and isopropyl myristate(IPM) on flurbiprofen(FP) patches in white rabbits, and to explore the correlation between in vitro and in vivo permeability. Methods: The pharmacokinetic parameters of FP patches with different enhancers were calculated after topical application in rabbits, and a deconvolution method was employed to analyze the correlation between the in vitro and in vivo drug permeation. In vitro release experiment and attenuated total reflection-fourier transform infrared spectroscopy(ATR-FTIR) were introduced to explore the mechanisms of permeability promotion for the enhancers. Results: The in vivo penetration experiments displayed that TEN-C7 had notable promoting effect on the transdermal delivery of FP. Additionally, the in vivo results obtained were in good correlation with the in vitro data(R~2>0.878 3). The in vitro release experiment showed the enhancers could promote the drug release through the interaction with pressure sensitive adhesive. According to result of ATR-FTIR, the enhancers disrupted the lipid bilayer as well as affected the skin protein region thereby disturbing stratum corneum(SC) arrangement. Conclusion: TEN-C7 has significant penetration promotion effect in vitro and in vivo, and it is necessary to further extend its application.更多还原