Specific mechanical energy - An essential parameter in the processing of amorphous solid dispersions

Abstract

Specific mechanical energy (SME) is a frequently overlooked but essential parameter of hot-melt extrusion (HME). It can determine whether an amorphous solid dispersion (ASD) can be successfully processed. A minimum combination of thermal input and SME is required to convert a crystalline active pharmaceutical product (API) into its amorphous form. A maximum combination is allowed before it or the carrier polymer chemically degrades. This has important implications on design space. SME input during HME provides information on the totality of the effect of various independent processing parameters such as screw speed, feed rate, and complex viscosity. If only these independent processing parameters are considered separately instead of SME, then important information would be lost regarding the interaction of these parameters and their ability to affect ASD formulation. A complete understanding of the HME process requires an analysis of SME. This paper provides a review of SME use in the pharmaceutical processing of ASDs, the importance of SME in terms of a variety of formulation qualities, and novel future uses of SME. Theoretical background is discussed, along with the relative importance of thermal and mechanical input on various nonsolvent ASD processing methods.

Keywords: Hot melt extrusion; Kinetisol solid dispersion; Nahme number; Noyes–Whitney; Stokes–Einstein; Viscous dissipation.