POLYMORPHIC STUDIES OF FLUCONAZOLE IN DIFFERENT CRYSTAL SOLVATE FORMS AND ITS IMPLICATION ON BCS SOLUBILITY AND DISSOLUTION

摘要

Fluconazole (anhydrate) is an anti-fungal agent which exists in various polymorphic forms. The present study is an attempt to obtain crystal solvates of fluconazole using various solvents and study its effect on polymorphic transformation and its implication on solubility and dissolution, fluconazole exhibits polymorphism and is poorly soluble in water, hence attempt was made to improve its solubility and dissolution. Crystal solvates of fluconazole were prepared in different solvents viz acetonitrile, methanol, propan-2-d and n-butanol. Polymorphic transformations were ascertained by subjecting the crystal solvates of fluconazole to BCS solubility, dissolution, FTIR, optical microscopy, DSC, SEM and X-ray powder diffraction (XRPD). Results indicated that the crystal solvates of propan-2-ol exhibited improved solubility and dissolution compared to other crystal solvates and pure drug. BCS based intrinsic solubility studies revealed that crystal solvates of propan-2-ol exhibited highest solubility at pH 1.2. FTIR studies revealed that the functional groups of fluconazole were found to be unaltered. Optical microscopy and scanning electron microscopy studies revealed morphological changes of crystal solvates, which indicates polymorphic changes of fluconazole. DSC of crystal solvates obtained from propan-2-ol revealed change to hydrate form, whereas XRPD study revealed crystal solvates of propan-2-ol were more crystalline in nature when compared with that of the pure drug.