Depending on the drug loading, the visual appearance of the polymer-drug extrudates differs significantly (Figure , Supporting Information Figure ). The samples with lower drug loadings have a bright yellow color, are transparent and possess a smooth surface. This was observed up to a drug loading of 60wt% for P1 and P2. Increasing the amount of drug in the sample further to 75wt% or 80wt% results in extrudates with a rough surface and residual heterogeneities, presumably residual crystalline drug particles, which are visible with the naked eye. Similar observations were made for the PVP and P(VP-co-VA) controlsthe samples containing 50wt% drug are bright yellow in color and transparent, whereas the samples containing 80wt% drug contained heterogeneities, resulting in opaque samples with a rough surface structure (Supporting Information Figure ). The optical observations of the drug loaded extrudates were corroborated by PXRD diffractograms (Figure ). After extrusion, the samples exhibit different patterns depending on their drug loading. For the samples containing P1 and a drug loading of 80wt%, the characteristic Bragg peaks of γ-IND are still present, while the diffuse halo is barely visible, indicating high residual crystallinity of the drug. Upon decreasing the drug loading to 75wt% and below, these characteristic peaks are no longer observed, suggesting successful preparation of ASDs. It is important to note, however, that PXRD is a bulk analysis method and, at the same time, as drug loading decreases the background noise increases relative to the drug loading. These factors make it challenging to rule out residual trace crystallinity. The ASD samples with P2, PVP and P(VP-co-VA) (Supporting Information Figure -S10) as excipients show an essentially identical behavior. Only the extrudates with the highest drug loading of 80wt% for all three polymers exhibit the characteristic Bragg peaks indicating the presence of γ-IND. Successful ASD preparation with various drug loadings and different preparation methods is well documented for both PVP and P(VP-co-VA). With IND as a model drug, spray dried ASDs with up to 85wt% and 70wt% drug loading were reported for PVP and P(VP-co-VA), respectively. DSC was used to study the thermal properties of the extrudates. As the solubility of the drug in the polymer matrix changes with increasing temperature, only the first heating cycle of the measurements was considered. For P1, interestingly, extrusion of the pure polymer alone changed its Tg. Before extrusion, the Tg of the polymer was 50 °C (Table ), while after extrusion, it dropped to 45 °C (Figure ), indicating the influence the processing method can have on the glass transition of an amorphous system. It is unlikely the lower T g is due to degradation during HME, as SEC measurements before and after the extrusion process resulted in identical elugrams (Supporting Information Figure ).