综合主成分分析法和皮肤电阻法对几种促透剂促透效果的比较

Comparison of the Penetration Promoting Effects of Several Transdermal Enhancers by Comprehensive Principal Component Analysis Method and Skin Resistance Method

关键词:  主成分分析  皮肤电阻法  促透剂  经皮给药  评价方法

Key words:  principal component analysis  skin resistance method  penetration enhancer  transdermal administration  evaluation method

摘要:

目的 建立一种简单有效的快速评价促透剂透皮吸收促进效果的方法，并比较综合主成分分析法和皮肤电阻法的促透剂评价结果。方法 以氨茶碱作为模型药物，氮酮、薄荷醇、冰片、油酸及其联用作为促透剂，SD大鼠背部离体皮肤作为渗透屏障，HPLC测定接收液中的药物浓度，计算累积渗透量、渗透系数、稳态流量、滞后时间和增渗倍数，运用综合主成分分析法对促透效果进行综合评价；测定在促透剂作用下的大鼠皮肤电阻随时间的变化，评价促透剂对皮肤的作用程度。结果 用Franz扩散池方法结合综合主成分分析法，得到对氨茶碱有促透效果的促透剂有油酸加冰片以及薄荷醇，且油酸加冰片的促透效果大于薄荷醇；用皮肤电阻法测得有促透作用的是油酸加冰片、薄荷醇加氮酮、薄荷醇、氮酮、油酸、冰片加氮酮以及薄荷醇加冰片，且作用程度依次递减。采用皮肤电阻法评价的促透效果与采用体外透皮吸收试验评价的结果基本平行(r=0.886 9)。结论 综合主成分分析法和皮肤电阻法都可以客观评价促透剂的效果，且2种方法具有明显的相关性。

Abstract:

OBJECTIVE To develop a simple and effective method to efficiently assess the effect arising from transdermal absorption of the penetration enhancer, and to compare the effect of the penetration enhancer assessed using the comprehensive principal component analysis method and the skin resistance method. METHODS In this study, aminophylline was adopted as a model drug, and azone, menthol, borneol, oleic acid and their combination were employed as the permeation enhancers. The isolated back skin of SD rats was applied as a permeation barrier. The drug concentration in the receiving solution was measured using HPLC. Moreover, cumulative permeability, permeability coefficient, steady flow rate, lag time and infiltration multiple were calculated, and the effect of permeability promotion was comprehensively assessed through a principal component analysis. The changes of skin resistance over time were measured to assess the effect arising from penetration enhancers on skin. RESULTS The results were achieved using the Franz diffusion cell method combined with the comprehensive principal component analysis method, indicating that oleic acid plus borneol and menthol had a penetration promoting effect on aminophylline, and the penetration promoting effect of oleic acid and borneol was higher than that of menthol. The penetration promoting substances measured by skin resistance included oleic acid plus borneol, menthol plus azone, menthol, azone, oleic acid, borneol plus azone and menthol plus borneol, and the effect degree decreased in descending order. The penetration promotion effect assessed by the skin resistance method was basically parallel to that assessed through the in vitro transdermal absorption experiment(r=0.886 9). CONCLUSION Both the integrated principal component analysis method and the skin resistance kinetics method are found to be capable of objectively assessing the effect of the penetration enhancer, and the two methods are obviously correlated with each other.