Comparison of four different in vitro systems to study the reservoir capacity of the stratum corneum

Four in vitro test systems were used to study the reservoir capacity of porcine stratum corneum (SC) for flufenamic acid and its drainage via penetration into the deeper skin layers: Franz diffusion cell using full thickness skin and split skin of 300 μm; Saarbruecken penetration model (SB) and intact porcine tissue (IP). Each skin sample was segmented 1, 4 and 21 h after application of an 'infinite dose' of flufenamic acid. The lipophilic drug was extracted from the SC and the deeper skin layers (viable epidermis and dermis) and determined using high-performance liquid chromatography (HPLC). For each test system, an increase in the drug amount in the deeper skin layers and the acceptor fluid, respectively, was observed in combination with a decreased amount in the SC with increasing time after application. The drainage of the SC reservoir was only reflected by a linear correlation of the drug amount in the SC with the amount in the deeper skin layers in the case of IP. The absolute drug concentrations previously detected in human skin in vivo and in vitro were compared with the present data, affording the best accordance in the case of IP.