Bifonazole: a missing case of polymorphism

Bifonazole, an imidazole-based antifungal drug, can be easily amorphized and crystallizes upon reheating at moderate scanning rate. Driven by recent results in literature reporting for this compound the appearance of polymorphism under different thermal histories, the present study presents an extensive calorimetric characterization of bifonazole in its crystalline and amorphous state. A rich scenario in crystallization behaviour has been found, implying that the behaviour observed on reheating scans can strongly depend on the previous thermal history and on the distribution in number and size of crystalline regions. In particular, the decrease in melting enthalpy during reheating, related to the increase of the heating rate, can be stated to be the result of a partial crystallization of the sample. Additionally, the temperature intervals more favourable to crystal nucleation and growth, respectively, have been determined, thanks to the choice of ad hoc time–temperature profiles. Finally, also the nucleation occurrence in time at high temperature has been investigated using a suitable DSC protocol. The overall results show how complex can be the cold-crystallization behaviour of a molecular liquid.