Melt-based screening method with improved predictability regarding polymer selection for amorphous solid dispersions
The predictability of preformulation screening tools for polymer selection in amorphous solid dispersions (ASD) regarding supersaturation and precipitation was systematically examined. The
API-polymer combinations were scaled up by means of hot-melt extrusion and spray-drying to verify the predictions. As there were discrepancies between a solvent-based screening and performance of
ASD, a new screening tool with improved predictability at minimal investments of time and material is presented. The method refinement resulted in a better correlation between the screening and
So far, a purely solvent-based screening was used which consisted of film casting by rapid solvent evaporation. This approach was improved by applying a heating step after film casting. Four
representative polymers were tested with two different model active pharmaceutical ingredients (API) under non-sink dissolution conditions. Polyvinylpyrrolidone (PVP) based polymers showed no
benefit towards pure API in the solvent-based screening but good supersaturation as ASD formulations. The extrudates with cellulose derivatives hydroxypropylmethylcellulose acetate succinate
(HPMCAS) and cellulose acetate phthalate (CAP) showed lower supersaturation than predicted by the solvent-based screening but performed especially well as spray-dried dispersions (SDD).
False negative results for PVP-co-vinyl acetate (PVP-VA64) could be avoided by using the new melt-based screening. Furthermore, comparing the results from the two different screening methods
allowed predicting the performance of extrudates vs. SDD with cellulose derivatives as polymeric excipients.