Resolving drug release mechanisms of amorphous solid dispersions using optical coherence tomography

This study presents an integrated approach utilising optical coherence tomography (OCT) to investigate the drug release mechanisms of hot-melt extruded (HME) amorphous solid dispersions (ASDs) of ritonavir and Soluplus®. Ritonavir-Soluplus® extrudates were prepared via HME using a twin-screw extruder and characterized during dissolution using a custom-designed 3D-printed flow cell, which enabled in-situ OCT imaging and continuous UV-vis monitoring of drug release. OCT provided high-resolution, time resolved visualization of structural transformations within the dissolving extrudates, while UV-vis spectroscopy quantified active pharmaceutical ingredient (API) release kinetics. Results revealed a multiphase dissolution mechanism involving sequential surface film formation, polymer swelling, delamination, and erosion. Increasing drug loading (10-30% w/w) produced marked effects on dissolution behaviour: formulations above 14% exhibited delayed release onset, extended swelling phases, and reduced overall release efficiency. OCT data showed that drug loadings above 14% led to slower erosion rates, greater swelling, and prolonged structural integrity, correlating with delayed UV-vis release profiles. Image processing using a machine learning segmentation model enabled quantitative extraction of sample cross-sectional area, confirming load-dependent swelling and erosion dynamics. Together, these findings establish a mechanistic link between structural evolution and release kinetics in HME ASDs and demonstrate the capability of OCT to provide real-time, non-destructive insight into solid dosage form dissolution. This methodology offers a powerful framework for optimizing ASD formulations and enhancing the predictive understanding of drug release mechanisms.