The influence of the lipid composition on drug permeation though stratum corneum-mimicking biomimetic artificial barriers

Accurate prediction of drug permeation through the stratum corneum is crucial for efficient preclinical development of topical formulations. In this study we investigated the suitability of two different stratum corneum-mimicking barriers (SCMBs) as predictive tools for evaluating the performance of topical formulations. For this purpose, we investigated hydrogels containing respectively three different APIs, i.e., caffeine, diclofenac, and ibuprofen as model formulations. Prior to in vitro permeation studies, the rheology, spreadability and swelling properties of the gels were characterized. Drug release kinetics were also investigated, following the USP dissolution test for semisolids. In vitro permeation studies across SCMBs highlighted the predominant role of API molecular properties on the permeation across lipid-based barriers, particularly API partitioning/hydrophilicity and molecular size. Interestingly, the results highlighted the crucial role of the lipid composition of the SCMB and, specifically, the ceramides content, in the API permeation kinetics. Ex vivo permeation studies evidenced distinct differences in permeation behavior between SCMBs and biological skin models, where the latter showed higher barrier resistance and lower permeation, in line with their more complex structural organization. Overall, the two artificial membranes tested represent reliable and predictive systems for early-stage topical formulation screening.