LAUSR

Graphical abstract Figure. No Caption available. Abstract In spite of the large research efforts in the past two decades, it is still difficult, if possible at all, to predict what manufacturing technology will lead to the best amorphous solid dispersions (ASDs) in terms of drug to polymer ratio (“drug loading”) and physical stability. In general, ASDs can be prepared by solvent based methods, heat based methods and mechanochemical activation. In the current study, one manufacturing technique per category was selected: spray drying, hot melt extrusion and cryo‐milling, respectively. These processes were compared for their capability to formulate high drug loaded ASDs. High drug loadings may allow decreasing the pill burden and/or reducing dosage size, which both increase the therapeutic compliance. A fast crystallizer, naproxen, in combination with PVP K25, PVP‐VA64, HPMC and HPMC‐AS was used as a model system. Clear differences in the physical structure of the ASDs were observed. Our data indicate that not only the drug loading is dependent on the manufacturing process, but also the carrier that is able to incorporate the highest drug loading. This suggests that a carrier should be selected not only as function of the API, but also as function of the manufacturing process. Overall, hot melt extrusion showed to be most suited to reach high drug loadings for these naproxen‐polymer combinations. This was in agreement with our finding that heat is an important energy input for mixing.