Solid state amorphization of pharmaceuticals

Abstract

Amorphous solids are conventionally formed by supercooling liquids or by concentrating noncrystallizing solutes (spray-drying and freeze-drying). However, a lot of pharmaceutical processes may also directly convert compounds from crystal to noncrystal which may have desired or undesired consequences for their stability. The purpose of this short review paper is (i) to illustrate the possibility to amorphize one compound by several different routes (supercooling, dehydration of hydrate, milling, annealing of metastable crystalline forms), (ii) to examine factors that favor crystal to glass rather than crystal to crystal transformations, (iii) to discuss the role of possible amorphous intermediates in solid-solid conversions induced by milling, (iv) to address the issue of chemical stability in the course of solid state amorphization, (v) to discuss the nature of the amorphous state obtained by the nonconventional routes, (vi) to show the effect of milling conditions on glasses properties, and (vii) to attempt to rationalize the observed transformations using the concepts of effective temperature introduced in nonequilibrium physics.