Development and validation of a Parallel Artificial Membrane Assay Permeation model for personal care formulations

离体人皮肤是使用体外皮肤渗透研究评估局部制剂的最优选方法。使用切除的人类皮肤的主要挑战是（1）难以获得皮肤样品和（2）样本内和样本间的可变性（Dick和Scott，1992; Schmook等人，2001年）。已经开发了几种替代模型用于预测化学品的皮肤渗透。这些模型之一，皮肤平行人工膜渗透试验（PAMPA）模型已被研究用于预测皮肤渗透的几种分子。皮肤PAMPA膜本质上是一种过滤基质，涂有排列在96孔板中的合成脂质，可以快速高通量筛选化合物。最近，UCL小组对咖啡因、布洛芬和烟酰胺在皮肤PAMPA膜和人体组织中的渗透进行了有限剂量条件下的比较研究。与用动物组织进行的常规体外渗透研究相比，在PAMPA模型中观察到随时间渗透的活性物质的累积量具有非常好的相关性。然而，重要的是要注意到，迄今为止，在PAMPA模型中已经研究了非常简单的配方，例如单一或二元溶剂体系。

Excised human skin is the most preferred approach for the assessment of topical formulations using in vitro skin permeation studies. The major challenges in using excised human skin are (1) the difficulty in sourcing the skin samples and (2) intra- and inter-specimen variability (Dick and Scott, 1992; Schmook et al., 2001). Several alternative models have been developed for prediction of skin permeation for chemicals. One of these models, the skin Parallel Artificial Membrane Permeation Assay (PAMPA) model has been investigated for prediction of the skin permeation of several molecules. The skin PAMPA membrane is essentially a filter substrate coated with synthetic lipids arranged in 96-well plate and allows for rapid and high-throughput screening of compounds. Recently, the UCL group has performed comparative studies for permeation in the skin PAMPA membrane and in human tissue under finite dose conditions for caffeine, ibuprofen and niacinamide. Very good correlations were observed for cumulative amounts of active permeated over time in the PAMPA model compared with conventional in vitro permeation studies with animal tissue. However, it is important to note that to date, very simple formulations e.g. single or binary solvent systems have been investigated in the PAMPA model.