College of Engineering, China Agricultural University, P.O. Box 191, 17 Qing-Hua-Dong-Lu, Beijing 100083, China.
Department of Chemical and Process Engineering, University of Surrey, Guildford GU27XH, UK.
J Pharm Sci. 2019 Sep;108(9):3003-3010. doi: 10.1016/j.xphs.2019.04.027. Epub 2019 May 2.
Despite a number of studies showed that hair follicular pathway contributed significantly to transdermal delivery, there have been limited studies on the diffusion properties of chemicals in sebum. Here, the diffusion property of 17 chemical compounds across artificial sebum has been measured using diffusion cell. The diffusion flux showed 2 types of distinctive behaviors: that reached steady state and that did not. Mathematical models have been developed to fit the experimental data and derive the sebum diffusion and partition coefficients. The models considered the uneven thickness of the sebum film and the additional resistance of the unstirred aqueous boundary layer and the supporting filter. The derived sebum-water partition coefficients agreed well with the experimental data measured previously using equilibrium depletion method. The obtained diffusion coefficients in artificial sebum only depended on the molecular size. Change in pH for ionic chemicals did not affect the diffusion coefficients but influenced their diffusion flux because of the change of sebum-water partition coefficients. Generally, the measured diffusion coefficients of chemicals in artificial sebum are about one order of magnitude higher than those in the stratum corneum lipids, suggesting the hair follicle might have a non-negligible contribution to the overall permeation.
尽管有许多研究表明毛囊途径对经皮给药有重要贡献，但关于皮脂中化学物质的扩散性质的研究有限。在这里，使用扩散池测量了 17 种化学物质在人工皮脂中的扩散性质。扩散通量表现出 2 种不同的行为：达到稳定状态和未达到稳定状态。已经开发了数学模型来拟合实验数据并得出皮脂扩散和分配系数。该模型考虑了皮脂膜不均匀的厚度以及未搅动水边界层和支撑滤器的额外阻力。推导出的皮脂-水分配系数与先前使用平衡耗竭法测量的实验数据吻合良好。在人工皮脂中获得的扩散系数仅取决于分子大小。离子化学物质的 pH 值变化不会影响扩散系数，但会由于皮脂-水分配系数的变化而影响其扩散通量。一般来说，在人工皮脂中测量的化学物质的扩散系数比在角质层脂质中的扩散系数高约一个数量级，这表明毛囊可能对整体渗透有不可忽视的贡献。
