Interrelation of permeation and penetration parameters obtained from in vitro experiments with human skin and skin equivalents

In a comparative study, two different in vitro cutaneous test systems were examined: (1) The Franz diffusion cell (FD-C), a test system to study drug permeation through the skin and to obtain data like steady state flux and l ag time as well as permeability and diffusion coefficients. (2) The Saarbru ecken penetration model (SB-M), a test system to investigate drug penetrati on into different skin layers and after varying incubation times to acquire values about the quasi steady state drug amounts in the stratum corneum (S Q. Three drug concentrations (0.9, 0.45 and 0.225%) of a lipophilic model d rug preparation, flufenamic acid in wool alcohols ointment, were applied on the skin's surface using 'infinite dose' conditions. Trypsin-isolated SC, heat-separated epidermis, full-thickness skin and reconstructed human skin (RHS) served as skin membranes in the FD-C, while the SB-M experiments were only carried out using full-thickness skin. Increasing steady state flux d ata and m(ss) values (steady state drug amount in the SQ were detectable af ter the application of rising drug amounts. Concerning the permeability of the used skin membranes in establishing barrier properties, the following r ank order was observed: RHS > SC greater than or equal to epidermis > full skin. The flux data of the FD-C experiments for isolated SC, separated epid ermis and RHS were linearly related with the in., values of the SB-Nl inves tigations, allowing a direct comparison of permeation with penetration para meters. Concerning the drug amount in the SC, previous investigations succe eded in the establishment of an in vivo/in vitro correlation. Based on the results presented here, the prediction of drug amounts present in the SC af ter different incubation times in vivo is now possible after penetration as well as penetration experiments using the lipophilic model drug preparatio n, flufenamic acid in wool alcohols ointment. (C) 2001 Elsevier Science B.V . All rights reserved.