| Abstract |
Screening of pyrazinamide polymorphs was carried out by crystallization from solvents differing in polarity and hydrogen bonding ability and also by sublimation and lyophilization. Pure samples of polymorphs alpha, delta, and gamma could be prepared and mixtures of the beta form with one of the other polymorphs were also produced. These forms were fully characterized by infrared spectroscopy and two main profiles registered in file N-H stretching vibration region, clearly distinguishing polymorphs encompassing it dimeric pierazinimide unit, alpha, beta, and delta, and where the dimer does not exist, the gamma one. The thermal behavior of pyrazinamide polymorphs was also investigated using differential scanning calorimetry (DSC) and polarized light thermal microscopy, Supported by powder X-ray diffraction and infrared spectroscopy. The alpha, beta, and d forms give rise to healing to the Y form, in endothermic transitions, with some superheating being observed, Also, the DSC peaks display an irregular shape. These observations suggest kinetic hindering of the solid-solid transitions. An endothermic phase transition of the delta form to the alpha one was observed only for samples seeded with this latter polymorph. The relative stability of the four pyrazinamide polymorphs was derived from the experimental observations. |
