Microdiffusiometry: From Interfacial Diffusion Studies to Sustainable Mechanistic Drug Development

The increasing complexity of modern enabling formulations is progressively challenging the predictive capability of conventional in vitro dissolution test, which mainly rely on macroscopic and homogeneous experimental conditions. In contrast, drug transport is fundamentally governed by localized diffusion and interfacial phenomena occurring within unstirred aqueous boundary layers. In this context, localized UV–Vis spectroscopy, also referred to as microdiffusiometry, has emerged as a novel analytical approach for the direct experimental characterization of interfacial transport processes. Introduced in in 20181, this technique enables time-resolved monitoring of drug diffusion under unstirred conditions and quantitative extraction of mechanistic transport parameters through Fick-based diffusion modelling. Beyond its mechanistic relevance, microdiffusiometry represents a highly sustainable analytical strategy. The miniaturized experimental setup requires very small sample volumes, limited solvent consumption, reduced laboratory waste, and minimal energy input compared to conventional screening methodologies. Over the years, microdiffusiometry has been successfully applied to investigate drug release from complex formulations, mucus interactions, and free drug fractions in colloidal systems. The presentation summarizes the evolution, applications, and future potential of microdiffusiometry as a green and mechanistically driven analytical platform for next-generation sustainable drug development.