Phenomenology of crystalline polymorphism

The stability hierarchy of crystalline polymorphs is often determined on the basis of limited calorimetric data even when other useful data such as specific volumes may be available. This may lead to wrong conclusions or an incomplete picture of the stability behavior of a compound and may be problematic in many applications, for example for pharmaceuticals. Therefore, the topological approach has been applied to the pharmaceutical FK664, which exhibits crystalline dimorphism, using heat- and work-related thermodynamic data to obtain a pressure-temperature phase diagram and elucidate its phase behavior. The approach leads to the conclusion that FK664 is overall monotropic with form B the most stable solid phase. In other words, form A does not have a stable domain for any pressure-temperature coordinate. The case of FK664 demonstrates that making use of the full available thermodynamic data set in combination with statistical information of the phase behavior of small organic molecules and classical thermodynamics leads to a sound evaluation of the stability hierarchy for crystalline dimorphism.