Real-time, non-invasive monitoring of inhalable powder dissolution using optical coherence tomography.

Accurate characterisation of dissolution behaviour is critical for understanding and optimising the performance of inhalable pharmaceutical powders, yet existing in vitro dissolution methods are often labour-intensive and limited in their ability to capture transient dissolution dynamics under physiologically relevant conditions. In this study, an optical coherence tomography (OCT)-based refractometric approach is developed and validated as a quantitative, time-resolved method for monitoring dissolution in situ without liquid sampling. A custom dissolution cell incorporating a dedicated optical interrogation region was integrated with an OCT system to continuously measure dissolution-induced optical path length changes, from which local refractive index changes were estimated. The method was applied to fine and coarse lactose grades (with different median particle sizes), commercial mannitol, and in-house lactose-salbutamol sulphate blends. The obtained dissolution profiles were validated against standard analytical methods, demonstrating strong agreement in both temporal trends (Pearson r = 0.92; Spearman ρ = 0.93) and excellent linearity between OCT-measured refractive index and known concentration (linear regression R2 > 0.99) for lactose powder. Differences in dissolution behaviour arising from powder properties (e.g., particle size) and hydrodynamic conditions (e.g., agitation rate) were resolved across the investigated formulations, demonstrating sensitivity to powder properties and hydrodynamic effects. Overall, the proposed method provides a robust, non-destructive framework for real-time analysis of transient and equilibrium dissolution behaviour, well suited to rapid batch-to-batch screening and dissolution studies.