Influence of Drug Properties, Formulation Composition, and Processing Parameters on the Stability and Dissolution Performance of Amorphous Solid Dispersions-Based Tablets.

Abstract

Polymeric-based amorphous solid dispersions (ASDs) represent a widely employed strategy for enhancing the oral bioavailability of poorly water-soluble drugs, but their successful implementation in solid dosage forms requires careful optimization of both formulation composition and compaction parameters. In this study, the performance of polymeric-based ASD tablets were investigated using two model active pharmaceutical ingredients (APIs) with distinct glass-forming abilities (GFAs) and physicochemical characteristics: (1) indomethacin (IND, a good glass former) and (2) carbamazepine (CBZ, a poor glass former). ASDs were prepared at various API-to-polyvinylpyrrolidone (PVP) ratios (10:90, 20:80 and 40:60 w/w) and incorporated into round-shaped tablets at different ASD loadings (20% and 50% w/w). The impact of compaction pressure and dwell time on the mechanical properties, disintegration, and supersaturation performance was assessed, both immediately after preparation and following three months of storage at 25 °C and 60% relative humidity. Solid-state analysis confirmed the amorphous state of the APIs and revealed the development of API-polymer molecular interactions. Supersaturation studies under non-sink conditions demonstrated that dissolution behavior was strongly influenced by drug loading, polymer content, and compaction conditions, with CBZ formulations exhibiting faster release but greater susceptibility to performance loss during storage. The comparative evaluation of IND and CBZ highlights the critical role of API properties in determining the physical stability and dissolution performance of ASD tablets, underscoring the need for API-specific design strategies in ASD-based formulation development.