A Review of Various Manufacturing Approaches for Developing Amorphous Solid Dispersions

Abstract

In recent years amorphous solid dispersions (ASD) has gained a tremendous response for improving the solubility of poorly water-soluble drug substances. Despite the stability challenges, various ASD commercial products have been successfully launched into the market over the last two decades. Among various manufacturing approaches, hot melt extrusion (HME) and spray drying techniques have attracted industries attributing to their simple manufacturing processes. In addition, KinetisolÒ, a solvent-free approach, is also being most widely investigated for developing ASDs since the thermal exposure time of the formulations is significantly less compared with the hot melt extrusion process. KinetisolÒ can be employed for developing ASDs of thermolabile drug substances. Another solvent-based technique, electrospinning, is also employed for developing nanofibers-based ASD. However, much research is warranted for the electrospinning process before implementing it in commercial manufacturing. Various critical factors such as drug-polymer solubility, the solubility of the drug in the polymer, drug-polymer interactions, type of manufacturing process, and storage conditions need to be considered for developing a stable and robust ASD formulation. This review mainly focuses on the most advanced manufacturing technologies of ASDs, namely HME, spray drying, KinetisolÒ, and electrospinning, along with a note on the various critical factors that affect the stability of ASD formulations. Keywords: amorphous solid dispersions; hot melt extrusion; spray drying; KinetisolÒ; electrospinning