The bioequivalence of pharmaceutical formulations is typically demonstrated by assessing the pharmacokinetics (PK) of a generic product relative to a reference listed drug (RLD) product. However, for topical products applied to the skin, it has been historically challenging to quantify the drug concentration at the target site of action, and therefore the applicability of the PK-based approach has been limited. Here, we present a novel approach based on stimulated Raman scattering imaging and data processing via deep learning for image feature extraction and automated analysis of cutaneous PK parameters, which also enables the imaging of drug distribution in real time.
Confocal Raman spectroscopy (CRS) enables the real-time profiling of substances penetrating to the skin without sample pre-treatment or labelling. Until now, CRS had been used as a semi-quantitative method, which posed challenges for evaluating topical formulations and assessing bioequivalence. We present a novel approach of CRS for quantitative analysis of skin delivery. The quantitative CRS in vivo has been correlated with the well-established in vitro Franz-diffusion experiments, indicating the potential of CRS for determining skin delivery. We anticipate CRS providing a rapid and non-invasive method that will be an attractive alternative to the clinical studies currently used in bioequivalence testing.
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