Milling-Induced Disorder of Pharmaceuticals: One-Phase or Two-Phase System?

During milling, components are subjected to shear and tensile stresses, which can result in physical phase transformations. The purpose of the work described in this report is to understand the pathway by which two test compounds, d-salicin and γ-indomethacin, undergo a crystalline to amorphous transformation during cryomilling. The results show that the transformation cannot be described by a standard one-phase or two-phase disordering mechanism. In the one-phase model, a continuous set of states exist, linking perfect crystalline with completely amorphous material, whereas the two-phase model of disorder depicts the material as a binary mixture of crystalline and amorphous fractions. Instead, a model is proposed where two one-phase regions, defected crystalline and amorphous regions, are separated by a distinct transition.