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

使用体外皮肤渗透研究来评估外用制剂时，切取的人体皮肤是最受欢迎的方法。使用离体人皮肤的主要挑战是(1)获取皮肤样本的困难以及(2)样本内和样本间的变异性(Dick和Scott，1992；Schmook等人，2001)。已经开发了几种可供选择的模型来预测化学品的皮肤渗透性。在这些模型中，皮肤平行人工膜渗透试验(PAMPA)模型被用来预测几种分子的皮肤渗透。皮肤PAMPA膜本质上是一种由96孔板中排列的合成脂类包裹的过滤基质，允许快速和高通量地筛选化合物。最近，UCL小组对咖啡因、布洛芬和烟酰胺在有限剂量条件下在皮肤Pampa膜和人体组织中的渗透进行了比较研究。与传统的动物组织体外渗透研究相比，在PAMPA模型中观察到随时间累积的有效渗透量具有很好的相关性。然而，值得注意的是，到目前为止，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.