Cocrystals of itraconazole with amino acids: Screening, synthesis, solid state characterization, in vitro drug release and antifungal activity

Itraconazole (ITZ) is an antifungal compound and a weak base with log P of 6.2 with an extremely low aqueous solubility 5 μg/ml, and high permeability, and consequently belonging to Biopharmaceutical Classification System Class II. The objectives of present investigation were to determine Hansen solubility parameters, synthesis, solid state characterization, in vitro drug release and antifungal activity of itraconazole cocrystals. The different formulations were prepared by neat and cocktail cogrinding with different amino acids like aspartic, glycine, proline, serine and succinic acid as a coformer. The prepared formulations were characterized in terms of saturation solubility, infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), in vitro dissolution studies and in vitro antifungal activity. In DSC studies ITZ amino acids cocrystals showed depression in melting point, whereas difference in δ values were below 5 and the prepared complex can be called as cocrystals. The results revealed considerable changes in the IR peaks of Itraconazole in the prepared co-crystals when compared to pure drug thereby indicating the presence of hydrogen bonding and π–π bonding in the newly formed cocrystals. Cocrystallization of Itraconazole resulted in five novel cocrystal forms including four cocrystals and one cocktail cocrystal with improved in vitro antifungal activity.