Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267.
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
J Pharm Sci. 2019 Jan;108(1):350-357. doi: 10.1016/j.xphs.2018.08.014. Epub 2018 Aug 27.
The effectiveness of skin penetration enhancers and the enhancer concentration required for effective skin permeation enhancement are difficult to predict. A comprehensive quantitative structure-enhancement relationship of chemical penetration enhancers for skin permeation is not currently available. The present study (a) investigated the relationship between skin permeation enhancement and chemical enhancer concentration and (b) examined a simple quantitative structure-enhancement relationship for predicting skin permeation enhancement to guide enhancer formulation development. In the present analysis, data from previous skin permeation studies that used the symmetric/equilibrium configuration and skin parallel pathway model were summarized to determine the relationship between enhancement factor and enhancer concentration. Under the equilibrium conditions, semilogarithmic linear relationships between enhancement factor (E) and enhancer aqueous concentration (C) were observed and an enhancer potency parameter (α) was defined. A correlation between the potency parameter α and enhancer octanol/water partition coefficient (Koct) was obtained. The enhancement factor relationship was derived: Log E = 0.32 ∙ C ∙ Koct. The results suggest that a "threshold" of (C ∙ Koct) > 0.5 M is required to induce effective skin permeation enhancement under these conditions. Consistent with the analyses in previous studies, the data suggest that octanol represents the skin barrier microenvironment for the penetration enhancers.
透皮增强剂的效果及其实现有效透皮增强所需的浓度难以预测。目前还没有关于化学透皮增强剂的综合定量结构-增强关系。本研究（a）调查了透皮增强与化学增强剂浓度之间的关系，（b）考察了一种简单的定量结构-增强关系，以预测透皮增强，从而指导增强剂配方的开发。在本分析中，总结了先前使用对称/平衡构型和皮肤平行途径模型的透皮研究的数据，以确定增强因子与增强剂浓度之间的关系。在平衡条件下，观察到增强因子（E）与增强剂水相浓度（C）之间的半对数线性关系，并定义了增强剂效力参数（α）。获得了效力参数α与增强剂辛醇/水分配系数（Koct）之间的相关性。推导出增强因子关系：Log E = 0.32 ∙ C ∙ Koct。结果表明，在这些条件下，需要（C ∙ Koct）> 0.5 M 的“阈值”才能诱导有效透皮增强。与先前研究中的分析一致，数据表明辛醇代表了用于透皮增强剂的皮肤屏障微环境。
