The physical stability of amorphous solid dispersions (ASD) of active pharmaceutical ingredients (APIs) of high glass forming ability (GFA class III) is generally expected to be high among the scientific community. In this study, the ASD of ten-selected class III APIs with the two polymers, PVPVA 64 and HPMC-E5, have been prepared by spray-drying, film-casting, and their amorphicity at T0 was investigated by modulated differential scanning calorimetry and powder X-ray diffraction. It was witnessed that only five out of ten APIs form good quality amorphous solid dispersions with no phase separation and zero crystalline content, immediately after the preparation and drying process. Hence, it was further established that the classification of an API as GFA class III does not guarantee the formulation of single phase amorphous solid dispersions.

The aim of this paper was to investigate whether a surface coating technique could be developed that can predict the phase behavior of amorphous solid dispersions (ASDs) coated on beads. ASDs of miconazole (MIC) and poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) in methanol (MeOH) were studied as a model system. First, the low crystallization tendency of the model drug in MeOH was evaluated and confirmed. In a next step, a drug loading screening was performed on casted films and coated beads in order to define the highest possible MIC loading that still results in a one-phase amorphous system. These results indicate that film casting is not suitable for phase behavior predictions of ASDs coated on beads. Therefore, a setup for coating a solid surface was established inside the drying chamber of a spray dryer and it was found that this surface coating technique could predict the phase behavior of MIC-PVP-VA systems coated on beads, in case an intermittent spraying procedure is applied. Finally, spray drying was also evaluated for its ability to manufacture high drug-loaded ASDs. The highest possible drug loadings that still result in a one-phase amorphous system were obtained for bead coating and its predictive intermittent surface coating technique, followed by spray drying and finally by film casting and the continuous surface coating technique, thereby underlining the importance for further research into the underexplored bead coating process.