Thermoanalytical study of polymorphic transformation in Fluconazole drug

Polymorphic transformation in Fluconazole (I) drug has been studied employing differential scanning calorimetry (DSC), X-ray diffraction and FT-IR techniques. Fluconazole (I) exhibited the sharp melting point at 138.4 °C. Considerable under cooling was, however, observed for the drug during cooling. No indication of freezing of molten Fluconazole (I) was evident in the DSC curve recorded up to a temperature of 25 °C in the cooling cycle. Reheating of the sample obtained after cooling, produced the DSC pattern much different compared to that obtained in the first heating and consisted of a sharp exothermic peak beginning at 81 °C preceding the twin endothermic peak with an onset temperature of 135.3 °C. In addition to these two peaks, a small endothermic peak was also observed around 31 °C, which could be attributed to a glass transition with an associated relaxation. The precise glass transition temperature derived from the data collected from six different independent experiments was found to be (31.67±0.13) °C. X-ray diffraction pattern of the Fluconazole (I) indicated that the as received sample was crystalline. The molten Fluconazole on cooling, however, produced a glassy amorphous mass. The amorphous product on heating to temperature >81 °C transformed to Fluconazole (II) which subsequently changed to Fluconazole (I) prior to melting. The split endothermic peak beginning at 135.3 °C recorded for the solidified Fluconazole sample is consistent with the observations made by X-ray diffraction. The observations made by employing DSC and X-ray diffraction were corroborated by FT-IR data on the samples isolated at different stages in the experiments.