Confocal Raman Spectroscopy for Assessing Bioequivalence of Topical Formulations

Abstract

The evaluation of bioequivalence (BE) for topical dermatological drug products is challenging, and there has been significant interest from regulatory authorities in developing new BE methodologies in recent years. Currently, BE is demonstrated by comparative clinical endpoint studies; these are costly and time-consuming and often lack sensitivity and reproducibility. Previously, we reported excellent correlations between in vivo Confocal Raman Spectroscopy in human subjects and in vitro skin permeation testing (IVPT) with the human epidermis for skin delivery of ibuprofen and a number of excipients. The aim of the present proof-of-concept study was to evaluate CRS as a method to assess BE of topical products. Two commercially available formulations, Nurofen Max Strength 10% Gel and Ibuleve Speed Relief Max Strength 10% Gel, were selected for evaluation. Delivery of ibuprofen (IBU) to the skin was determined in vitro and in vivo by IVPT and CRS, respectively. The formulations examined were found to deliver comparable amounts of IBU across the skin over 24 h in vitro (p > 0.05). Additionally, the formulations resulted in similar skin uptake values measured with CRS in vivo, either at 1 h or 2 h after application (p > 0.05). This is the first study to report the capability of CRS for the demonstration of BE of dermal products. Future studies will focus on the standardisation of the CRS methodology for a robust and reproducible pharmacokinetic (PK)-based evaluation of topical BE.