Exploring the Relationship Between Stability and Dynamics in Polymer-Based Amorphous Solid Dispersions for...

Mixing polymeric excipients with drugs in amorphous solid dispersions (ASD) is known to enhance the bioavailability of drugs by inhibiting their recrystallisation. However, the mechanisms underlying stabilisation remain not fully understood. This study aims to improve our understanding of the role of dynamics, particularly the molecular movements that drive instabilities, through investigations of ASD made of Polyvinylpyrrolidone (PVP K12) and a model drug, Terfenadine. The analyses combine temperature modulated differential scanning calorimetry (MDSC) and dielectric relaxation spectroscopy. The results reveal that the produced ASDs are supersaturated with Terfenadine, regardless of the content, and that PVP slows down the dynamics of the blends, limiting the recrystallisation of the drug during heating. Although the ASDs appear homogeneous based on thermal analysis with a single glass transition consistently detected by MDSC, the investigation of the dynamics reveals a dissociation of the main relaxation into two components for PVP contents below 30 wt.%. This dynamic heterogeneity suggests a structural heterogeneity with the coexistence of two amorphous phases of different compositions, each characterised by its own dynamics. The complex evolution of these dynamics under recrystallisation is rationalised by the confrontation with the phase and state diagram of Terfenadine/PVP blends established by MDSC.