Abstract：
We extended a mechanistic, physics-based framework of the dry down process, previously developed for liquids and electrolytes, to solids and coded it into the latest UB/UC/P&G skin permeation model, herein renamed DigiSkin. The framework accounts for the phase change of the permeant from dissolved in a solvent (liquid) to precipitated on the skin surface (solid). The evaporation rate for the solid is reduced due to lower vapor pressure for the solid state versus subcooled liquid. These vapor pressures may differ by two orders of magnitude. The solid may gradually redissolve and penetrate the skin. The framework was tested by simulating the in vitro human skin permeation of the 38 cosmetically relevant solid compounds reported by Hewitt et al., J. Appl. Toxicol. 2019, 1-13. The more detailed handling of the evaporation process greatly improved DigiSkin evaporation predictions (r2 = 0.89). Further, we developed a model reliability prediction score classification using diverse protein reactivity data and identified that 15 of 38 compounds are out of model scope. Dermal delivery predictions for the remaining chemicals have excellent agreement with experimental data. The analysis highlighted the sensitivity of water solubility and equilibrium vapor pressure values on the DigiSkin predictions outcomes influencing agreement with the experimental observations.
摘要：
我们扩展了一个机械师，基于物理的干涸过程框架，以前开发的液体和电解质，将其编码为最新的UB/UC/P&G皮肤渗透模型，在此更名为DigiSkin。骨架说明了渗透物从溶解在溶剂(液体)中到沉淀在皮肤表面(固体)上的相变。由于固态相对于过冷液体的较低蒸气压,固体的蒸发速率降低。这些蒸气压力可以相差两个数量级。固体可逐渐再溶解并渗透皮肤。通过模拟Hewitt等人报道的38种化妆品相关固体化合物的体外人皮肤渗透来测试框架。,J.应用。Toxicol.2019年1-13。蒸发过程的更详细处理极大地改进了DigiSkin蒸发预测(r2=0.89)。Further,我们使用不同的蛋白质反应性数据开发了模型可靠性预测得分分类,并确定38种化合物中有15种超出模型范围.其余化学品的真皮递送预测与实验数据具有极好的一致性。分析强调了水溶解度和平衡蒸气压值对DigiSkin预测结果的敏感性，这些结果会影响与实验观察结果的一致性。
