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Solvent and Crystallization Effects on the Dermal Absorption of Hydrophilic and Lipophilic Compounds

化学 渗透 角质层 乙醇 水溶液 色谱法 咖啡因 溶剂 肺表面活性物质 蒸馏水 有机化学 生物化学 医学 病理 内分泌学
作者
Lijing Xu,Gerald B. Kasting
出处
期刊:Journal of Pharmaceutical Sciences [Elsevier BV]
卷期号:113 (4): 948-960 被引量:2
标识
DOI:10.1016/j.xphs.2023.09.025
摘要

This study probes the mechanisms by which volatile solvents (water, ethanol) and a nonionic surfactant (Triton X-100) influence the skin permeation of dissolved solutes following deposition of small doses onto unoccluded human skin. A secondary objective was to sharpen guidelines for the use of these and other simple solvent systems for dermal safety testing of cosmetic ingredients at finite doses. Four solutes were studied - niacinamide, caffeine, testosterone and geraniol - at doses close to that estimated to saturate the upper layers of the stratum corneum. Methods included tensiometry, visualization of spreading on skin, polarized light microscopy and in vitro permeation testing using radiolabeled solutes. Ethanol, aqueous ethanol and dilute aqueous Triton solutions all yielded surface tensions below 36 mN/m, allowing them to spread easily on the skin, unlike water (72.4 mN/m) which did not spread. Deposition onto skin of niacinamide (32 μg·cm-2) or caffeine (3.2 μg·cm-2) from water and ethanol led to crystalline deposits on the skin surface, whereas the same amounts applied from aqueous ethanol and 2 % Triton did not. Skin permeation of these compounds was inversely correlated to the extent of crystallization. A separate study with caffeine showed the absence of a dose-related skin permeability increase with Triton. Permeation of testosterone (8.2 μg·cm-2) was modestly increased when dosed from aqueous ethanol versus ethanol. Permeation of geraniol (2.9 μg·cm-2) followed the order aqueous ethanol > water ∼ 2 % Triton >> ethanol and was inversely correlated with evaporative loss. We conclude that, under the conditions tested, aqueous ethanol and Triton serve primarily as deposition aids and do not substantially disrupt stratum corneum lipids. Implications for the design of in vitro skin permeability tests are discussed.
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