Mechanistic insights into drug loading effect on dissolution performance of Loratadine-Soluplus® amorphous solid...

Amorphous solid dispersions (ASDs) hold promising potential towards modulating the solubility of poorly soluble drugs. However, their use is limited by poor understanding of release mechanism and kinetics, especially with Soluplus®. In this study, we explored loratadine-Soluplus® ASDs with different drug loadings (DLs) from 3% to 15% to unveil drug content impact on dissolution, colloidal behavior, and surface composition. All formulations were fully amorphous and showed a single, composition-dependent glass transition temperature. Intrinsic dissolution testing revealed fast, nearly complete release and stable supersaturation for low-load ASDs (3-5% DL), while higher-load ASDs (10-15% DL) released more slowly, generated larger nanodroplets on liquid-liquid phase separation (LLPS), and showed precipitation upon standing. SEM imaging suggested similar surface morphology before and after partial dissolution, but EDX elemental analysis revealed congruent drug-polymer release at low DL and incongruent (polymer-first) release at high DL. These findings identify an optimum drug-loading window where ASD generates and sustains supersaturation status for loratadine, and highlight mechanistic links between DL, LLPS droplet size, and incongruent release that explain reduced performance at higher loadings.