Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267.
Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267.
J Pharm Sci. 2019 Feb;108(2):987-995. doi: 10.1016/j.xphs.2018.10.026. Epub 2018 Oct 26.
In a previous study investigating the relationships between solute physicochemical properties and solvent effects on skin permeation of solutes under finite dose conditions, urea was found to have the highest percent dose absorbed among the model solutes studied. The objective of this study is to probe the mechanism of the observed high skin permeation of urea at finite dose, in contrast to its permeability coefficient obtained under infinite dose condition. Skin permeation experiments were performed with Franz diffusion cells and human epidermal membrane. Dose-dependence and penetration enhancing effects of urea permeation were investigated. Tape stripping was performed. A small hydrophilic solute ethylene glycol with molecular weight similar to urea was studied for comparison. The results suggest that urea did not have penetration enhancing effect to enhance solute permeation across skin under the finite dose conditions. Tape stripping data are consistent with skin permeation mechanism of solute deposition and diffusion. The skin permeation behavior of urea could be attributed to its small molecular size. This suggests that, under the finite dose conditions examined in this study, solutes with molecular sizes similar to or less than urea and ethylene glycol could lead to high percent of skin absorption despite their hydrophilicities.
在之前的一项研究中，我们研究了在有限剂量条件下溶质物理化学性质与溶剂对溶质经皮渗透的关系，发现尿素是研究的模型溶质中吸收百分率最高的。本研究的目的是探讨在有限剂量下观察到的尿素高经皮渗透的机制，与在无限剂量条件下获得的渗透系数形成对比。实验采用 Franz 扩散池和人表皮膜进行皮肤渗透实验，研究了尿素渗透的剂量依赖性和渗透增强作用。进行了胶带剥离实验。为了进行比较，还研究了分子量与尿素相似的亲水性小溶质乙二醇。结果表明，在有限剂量条件下，尿素对增强溶质经皮渗透没有渗透增强作用。胶带剥离数据与溶质沉积和扩散的皮肤渗透机制一致。尿素的皮肤渗透行为可归因于其较小的分子量。这表明，在本研究中考察的有限剂量条件下，分子量与尿素和乙二醇相似或更小的溶质尽管具有亲水性，但仍可能导致皮肤吸收的百分率较高。
