Optimizing metrics for the assessment of bioequivalence between topical drug products

Purpose: Stratum corneum tape stripping post-application of a drug product followed by analysis of the active agent in this tissue layer is an approach being seriously considered for the comparative assessment of topical bioavailability. Key issues revolve around how best to perform this experiment and interpret the data. Methods: Using previously published results from a comparative study of three 0.025% tretinoin gel products, alternative data analysis approaches are presented that may render the technique more accessible to the evaluation of new and generic topical dosage forms. Results: For the tretinoin gel study, the conclusions for bioequivalence from measurements of drug levels at only one uptake and one clearance time were the same as those from the original study, which required measurements at eight different treatment times. Furthermore, comparisons of drug levels at one uptake and one clearance time discriminated differences in bioequivalence for clearance and uptake, which had previously been missed. Half-life estimates, derived from time course data of drug clearance, can be related to lag time for drug penetration through the SC. Conclusions: This new data analysis demonstrates that comparative bioequivalence might be assessed more easily.