Vacuum drum drying - A novel solvent-evaporation based technology to manufacture amorphous solid dispersions in comparison to spray drying and hot melt extrusion

Abstract

In this study, a novel solvent-evaporation based technology to manufacture amorphous solid dispersions (ASDs) called vacuum drum drying (VDD) was assessed in comparison to the conventional technologies hot-melt extrusion (HME) and spray drying (SD). Ritonavir (15%w/w) embedded in copovidone/sorbitan monolaurate was used to investigate the impact on the ASD quality, material properties and in-vitro dissolution. All ASDs met the critical quality criteria: absence of drug substance related crystallinity, residual solvents below ICH limit (SD, VDD) and degradation products within specification limits. Clear differences in material properties such as particle morphology and size distribution, powder densities and flowability properties were observed. Overall, the milled extrudate showed superior material properties in terms of downstream processability. The VDD intermediate performed slightly better in terms of flowability and electrostatic behavior compared to the spray dried while showing comparably unfavorable densities. However, the dissolution data suggested no significant difference between the ASDs prepared by HME, SD, and VDD and thus, no change in bioavailability is expected. In conclusion, the VDD technology might be a viable alternative to manufacture ASDs - especially for thermosensitive and shear-sensitive compounds with potential to process formulations with high solid loads and viscosities while exhibiting higher throughputs at a lower footprint.

Keywords: Amorphous solid dispersion; Hot-melt extrusion; Ritonavir; Spray drying; Vacuum drum drying.