不同促透剂对肝素钠肌醇烟酸酯乳膏透皮吸收影响

Effect of different penetration enhancers on transdermal absorption of heparin and inositol nicotinate cream with rabbit skin in vitro

目的探讨不同促透剂对肝素钠肌醇烟酸酯乳膏透皮吸收的影响。方法采用改良Franz扩散池,选择离体兔皮为渗透屏障,加入N-甲基吡咯烷酮(NMP)和肉豆蔻酸异丙酯(IPM)及氮酮等不同种类及浓度的促透剂,观察其对肝素钠肌醇烟酸酯乳膏透皮吸收的影响。结果肌醇烟酸酯在0.5~25.0μg/ml与峰面积呈良好的线性关系,回归方程为A=7 260.4C+1 214.9(r=0.999 1);精密度良好,肌醇烟酸酯峰面积为1.86%;5 h内稳定性良好,肌醇烟酸酯峰面积为1.26%;平均加样回收率为96.94%,肌醇烟酸酯峰面积为2.98%。对肝素钠肌醇烟酸酯乳膏中肌醇烟酸酯的促透作用强弱顺序依次为含3%氮酮的乳膏>含3%IPM的乳膏>含3%NMP的乳膏>未加促透剂的乳膏;不同用量氮酮的促透作用强弱顺序依次为3%氮酮>5%氮酮>1%氮酮。结论 3%氮酮对肌醇烟酸酯经皮吸收具有明显的促进作用,为肝素钠肌醇烟酸酯乳膏的处方的设计及新药的开发提供了依据。

Objective To investigate the effect of different penetration enhancers on the transdermal absorption of heparin and inositol nicotinate cream with rabbit skin in vitro. Methods Using modified Franz diffusion pool, rabbit skin was selected as the permeation barrier in vitro,different kinds and concentrations of penetration enhancers such as the N-methyl pyrrolidong（NMP） ,isopropyl myrisrate （IPM） and azone was joined, the transdermal absorption effect of heparin sodium inositol nicotinate cream was observed. Results There was a good linear relationship with the peak area within the range of 0. 5-25.0 μg/ml, and the equation was A = 7 260. 4C ＋ 1 214. 9 （ r = 0. 999 1 ） ; the precision was good, and the average recovery of inositol nicotinate was 96. 94% and the RSD was 2.98%. The order of different penetration enhancers of inositol nicotinate in the inositol nicotinate heparin sodium cream was：3% azone was more than 3% IPM which was more than 3% NMP which was more than none cream without penetration enhancer;the order of different dosage of azone was：3% azone was more than 5% azone which was more than 1% azone. Conclusion The 3% azone on inositol nicotinate percutaneous absorption has obvious role in promoting, and provide a basis for the design and development of new drugs for heparin sodium inositol nicotinate cream prescription.