In vitro/in vivo correlations in transdermal product development

Abstract

As per the US FDA's guidance for industry entitled ‘Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations’, in vitro–in vivo correlations (IVIVC) can be used to establish a dissolution test as a surrogate for human bioequivalence studies and certain scale-up and postapproval changes. However, at the present time, establishment of a transdermal IVIVC is not used to support biowaiver claims in late phases of clinical development or postapproval changes (major formulation changes, i.e., >10% changes in inactive ingredients) to the best of the authors’ knowledge. The value of developing an IVIVC for percutaneous drugs lies mainly in facilitating permeation testing of transdermal drug candidates and formulation performance optimization at much lower cost as compared with carrying out multiple in vivo studies. The present article will introduce the concept of transdermal IVIVC, outlining certain limitations to its applicability, in vitro and in vivo methods, regulatory product development requirements and the most common approaches to establish an IVIVC for a transdermal drug. Additionally, this article will also summarize some challenges and recent advancements in this field, along with selected academic examples of transdermal IVIVCs.