Polymorphic behavior of isonicotinamide in cooling crystallization from various solvents

In this work the nucleation of different polymorphs of isonicotinamide (INA) from different solvents has been studied. The metastable zone width of INA in cooling crystallization from five different solvents has been investigated and attempts have been made to reveal the link between the INA molecular self-association to the polymorphism of the nucleated crystals using ATR FT-IR (Attenuated Total Reflectance Fourier Transform Infrared) and Raman spectroscopy. Raman and IR spectra of INA dissolved in different solvents have demonstrated that the INA molecules might associate in different configurations, whereas, the link between the structure of the molecular self-association and the structure of the nucleated polymorph is complicated by the influence of INA concentration. This is consistent with our previous study with piroxicam. The cooling crystallization of INA from five different solvents resulted in two different polymorphs depending on the initial concentration of the solution. The results obtained in the present work showed that information about self-association of an API (Active Pharmaceutical Ingredient) in a given solvent is not sufficient to predict the polymorphic behavior in all scenarios.