Application of Melt Extrusion in the Development of a Physically and Chemically Stable High-Energy Amorphous Solid Dispersion of a Poorly Water-Soluble Drug

Formulation of active pharmaceutical ingredients (API) in high-energy amorphous forms is a common strategy to enhance solubility, dissolution rate and, consequently, oral bioavailability of poorly water-soluble drugs. Amorphous APIs are, however, susceptible to recrystallization and, therefore, there is a need to physically stabilize them as solid dispersions in polymeric carriers. Hot melt extrusion has in recent years gained wide acceptance as a method of choice for the preparation of solid dispersions. There is a potential that the API, the polymer or both may degrade if excessively high temperature is needed in the melt extrusion process, especially when the melting point of the API is high. This report details a novel method where the API was first converted to an amorphous form by solvent evaporation and then melt-extruded with a suitable polymer at a drug load of at least 20% w/w. By this means, melt extrusion could be performed much below the melting temperature of the drug substance. Since the gl...