Ritonavir release from spherical amorphous solid dispersions: prediction and observation

Solvent penetration was previously identified and modeled as the dominant rate-limiting step in ritonavir (RTV) release from amorphous solid dispersion (ASD) discs composed of poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA). In this study, drug release from discs was extended to spherical ASD particles. RTV/PVPVA ASDs with drug loadings of 5-25% were fabricated using vacuum compression molding (VCM) with a custom free-D mold to produce 1 mm and 5 mm spherical particles. The solvent penetration rates (dd/dt) across drug loadings (DLs), measured from discs under a microscope-enabled disc dissolution system (MeDDiS), were assumed to be an intrinsic and geometric-independent parameter and were directly applied to a spherical particle dissolution model. Dissolution studies were conducted under small-volume (20 mL) conditions for 1 mm particles and USP II conditions (900 mL) for 5 mm particles, including both single and multiple particle systems. Predicted dissolution profiles showed good agreement with experimental data across sphere diameter and the number of spheres undergoing dissolution. Overall, the results demonstrate the transferability of solvent penetration rate from discs to spherical particles and confirm that dissolution of RTV/PVPVA ASDs at low drug loadings [i.e., before reaching the limit of congruency (LoC)] was primarily governed by solvent penetration.