Thermodynamic scaling, amorphous solids

The amorphous phase is not usually a desirable state for the API because the formation process is more random and difficult to control than a crystallization. A second dispersed liquid phase is usually formed just prior to freezing and may coalesce or disperse under the influence of hydrodynamic forces in the crystallizer, making the process sensitive to micro-mixing effects on scale up. Amorphous solids also have significantly lower thermodynamic stability than related crystalline material and may subsequently crystallize during formulation and storage. Because of the non-uniformity of the amorphous solid it can more easily incorporate molecules other than the API, making purification less effective. 

Characterization of HME-based solid dispersions is not solely motivated by the need to directly measure physical failure. By extension, characterization tools and techniques provide insight into the fundamental properties which facilitate physical failure. For instance, measures of the thermodynamic properties and modes of motion associated with amorphous systems serve to better assess risk of physicochemical failure. Also, as was noted above, in several instances, although the material may be rendered amorphous, the differences in length scale of mixing may manifest as differences in performance, and, thus, characterization tools also inform process development. 

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