Clinical and Medical Sciences, University of South Australia, Adelaide, Australia and The Basil Hetzel Institute for Translational Health Research, Adelaide, Australia.
Diamantina Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Australia.
Int J Pharm. 2022 Nov 5;627:122114. doi: 10.1016/j.ijpharm.2022.122114. Epub 2022 Aug 13.
This study examined a number of factors that can impact the outcomes of in vitro human epidermal permeation coefficients for aliphatic alcohols and steroids, including receptor phase composition and study conditions. We determined experimentally the solubilities and IVPT permeation of a homologous series of C labeled aliphatic alcohols (ethanol, propanol, pentanol, heptanol, octanol and decanol) in different receptor fluids as recommended by Organisation Economic Co-operation and Development (OECD). We used human epidermal membranes at 25 °C and phosphate-buffered saline (PBS), 2 %w/v bovine serum albumin (2 %w/v BSA), 50 %w/v ethanol and 0.1, 2 and 6 %w/v Oleth-20 receptor phases. We also explored and confirmed the discrepancies between in vitro human epidermal permeability coefficients (k) and diffusion lag times for steroids from Scheuplein's group with our own work and that of others. The main reason for the observed differences is not clear but is likely to be multifactorial, including the effects of diffusion cell design, receptor phase solubility, unstirred receptor phase effects, epidermal membrane hydration, diffusion cell configuration, transport through appendageal pathways and steroid lipophilicity. We conclude with a summary of experimental conditions that should be considered in undertaking IVPT studies.
本研究考察了许多因素，这些因素可能会影响体外人体表皮渗透系数（用于脂族醇和甾体类药物）的结果，包括受体相组成和研究条件。我们按照经济合作与发展组织（OECD）的建议，用实验确定了一系列 C 标记的脂族醇（乙醇、丙醇、戊醇、庚醇、辛醇和癸醇）在不同受体液中的溶解度和 IVPT 渗透系数。我们在 25°C 下用人表皮膜和磷酸盐缓冲盐水（PBS）、2%w/v 牛血清白蛋白（2%w/v BSA）、50%w/v 乙醇以及 0.1%、2%和 6%w/v Oleth-20 受体相进行实验。我们还探索并证实了 Scheuplein 小组的体外人体表皮渗透系数（k）与甾体类药物扩散滞后时间之间的差异，这是我们自己的工作和其他人的工作。观察到差异的主要原因尚不清楚，但可能是多因素的，包括扩散池设计、受体相溶解度、未搅动受体相效应、表皮膜水合作用、扩散池结构、通过附属途径的传输和甾体类药物的亲脂性。我们总结了在进行 IVPT 研究时应考虑的实验条件。
