SRS-Microscopy and Deep-Learning: Novel Approach for Evaluation of Topical Bioequivalence

The bioequivalence (BE) of pharmaceutical formulations is typically demonstrated by assessing the pharmacokinetics (PK) of a generic product relative to a reference-listed drug (RLD) product. For drugs intended to act systemically, BE is normally assessed by estimating PK metrics from drug concentrations in the plasma; however, for topical products applied to the skin, it has been historically challenging to quantify the drug concentration at the target site of action in the skin, and therefore the applicability of the PK-based approach has been limited. Here, we present a novel approach for evaluating local tissue amounts of drug following topical application based on Stimulated Raman scattering (SRS) imaging and data processing via deep learning for image feature extraction and automated analysis of cutaneous PK parameters. The proposed approach also enables the imaging of drug distribution across the tissue in real time, which can additionally provide insights into the permeation pathways.