Pig ear skin ex vivo as a model for in vivo dermatopharmacokinetic studies in man

Objective. The objective was to investigate pig ear skin as a surrogate for human skin in the assessment of topical drug bioavailability by sequential tape-stripping of the stratum corneum (SC). The potential benefits of ex vivo investigations are manifold: ethical approval is not required, multiple replicate experiments are more easily performed, and toxic compounds can be evaluated. Materials and Methods. Ex vivo experiments on isolated pig ears were compared with in vivo studies in human volunteers. Four formulations, comprising the model drug, ibuprofen, in different propylene glycol (PG)-water mixtures (25:75, 50:50, 75:25 and 100:0), were compared. Results. Derived dermatopharmacokinetic parameters characterizing the diffusion and partitioning of the drug in the SC ex vivo were consistent with those in vivo following a 30-minute application period. Further, the non-steady-state ex vivo results could be used to predict the in vivo concentration profile of the drug across the SC when a formulation was administered for 3 h (i.e., close to steady-state). Conclusions. Taken together, the results obtained suggest that pig ear skin ex vivo has promise as a tool for topical formulation evaluation and optimization.