Study of process induced polymorphic transformations in fluconazole drug.
The polymorphic form-I of the fluconazole drug commonly crystallized from the solution phase could be obtained by the solid state transformation of form-II employing different process parameters. As received fluconazole-II drug melted at 138.4 degrees C. The molten drug undercooled almost to ambient temperature of 30 degrees C and solidified to a glassy mass which, on ageing for 48 h transformed to a white powder which could be identified as fluconazole-I. The same glassy mass on heating at 5 degrees C/min, without ageing, also underwent polymorphic transformation to fluconazole-I above 81 degrees C. The application of uniaxial pressure of 200 kg/cm2 on as received fluconazole-II sample also yielded form-I of the drug. This phase transformation was enhanced by the application of pressure (200 kg/cm2) on the as received sample aged for 36 months. The phase transformation was concluded from the difference in differential scanning calorimetric (DSC) curves of the original sample (form-II) and the products obtained by adopting the different processing routes. The DSC patterns of fluconozole-I obtained by different methods were found to be identical. The phase transformation in the as received drug (form-II) induced by different process parameters, concluded from the DSC data was corroborated by X- ray diffraction (XRD) studies and scanning electron microscope (SEM) photographs of the two polymorphic forms. The intrinsic dissolution rates of polymorphic form-I and -II and the influence of crystal habit on the drug dissolution process have also been studied.
Desai
Satish R
SR
Department of Chemistry, The Institute of Science, 15, Madam Cama Road, Mumbai-400 032, India.
Dharwadkar
Sanjiv R
SR
D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D015725:Fluconazole / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008968:Molecular Conformation; D012995:Solubility; D014961:X-Ray Diffraction
D000935:Antifungal Agents; D015725:Fluconazole