Considerations in the formulation of amorphous solid dispersions by hot melt extrusion

Hot melt extrusion is one of the most popular techniques for the manufacturing of amorphous solid dispersions (ASDs). Over few decades, it has transitioned from lab scale to commercial scale with various products in the market. The current review aims at summarizing various considerations in the formulation development of ASDs using HME. Various types of ASDs from Type I to Type IV are discussed along with the solid state of drug and polymeric carrier in each type. Also, various polymeric carriers used in ASDs are outlined along with information about their glass transition temperature, melting point, hygroscopicity and regulatory status. There are various mechanisms by which the polymeric carriers stabilize the amorphous form of drug in ASDs. These mechanisms are classified as crystallization inhibition, anti-plasticization, intermolecular interactions, and reduction of molecular mobility. These four mechanisms are discussed along with case studies. Finally, various considerations in the formulation of ASDs like, rationale selection of polymers, process design and optimization and stability testing with respect to formulation of ASDs using hot melt extrusion are discussed. In conclusion, the current state of formulating ASDs using HME are discussed and the need for restructuring the formulation approach is mentioned.