4-萜品醇脂肪酸酯对氟比洛芬贴剂的促渗透体内外相关性考察  

Correlation between In vitro and in vivo Penetration Enhancing Effect of 4-O-acylterpineol on Flurbiprofen Patches

作　　者：李燕[1] 司莉玲 王贺平 王春艳[1] 任博 赵利刚 Li Yan;Si Liling;Wang Heping;Wang Chunyan;Ren Bo;Zhao Ligang(Department of Pharmacy,Tangshan Maternal and Child Health Hospital,Hebei Tangshan 063000,China;Department of Pharmacy,Health Center of Xianshuigu Town,Jinnan District of Tianjin City;School of Pharmacy,North China University of Science and Technology)

机构地区：[1]唐山市妇幼保健院药剂科,河北唐山063000 [2]天津市津南区咸水沽镇卫生院药剂科 [3]华北理工大学药学院

出　　处：《中国药师》2021年第9期1721-1727,共7页China Pharmacist

基　　金：河北省自然科学基金项目(编号:H2019209254);国家自然科学基金项目(编号:81603039);华北理工大学杰出青年基金项目(编号:JQ201713)。

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(R2>0.8783);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。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(R2>0.8783).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.

关 键 词：氟比洛芬 4-萜品醇酯衍生物 促透剂 体内外相关性 促透机制 

分 类 号：R945[医药卫生—微生物与生化药学]