Relevance of equivalence assessment of topical products based on the dermatopharmacokinetics approach

Abstract

Common procedures to test bioequivalence of oral products, measuring the rate and extent of the obtained plasma levels, do not apply to drug products for topical use, which provide limited systemic absorption. Nowadays, clinical trials are still the goldenrule for the development of a generic topical product but, unfortunately, not many techniques are helpful for the specific investigation of in vivo topical absorption. Additionally, during early stages of pharmaceutical development, experimental procedures for demonstrating the quality by design of topical formulations are lacking. In some cases, the dermatopharmacokinetic characterization in healthy volunteers of the topical drug penetration by skin stripping has resulted to be a promising option. Recently, some authors have focused special efforts to enlighten all the capabilities of this approach. This short review tries to describe and discuss some aspects under optimization of dermatopharmacokinetics as is the influence of the formulation on drug performance, the parameter calculation and the experimental procedure for minimizing variability. All those aspects are nowadays in continuous improvement trying to define the place of dermatopharmacokinetics as a putative technique for avoiding clinical trials in topical generics development.