SOLVENT ASSISTED COCRYSTALLIZATION OF ITRACONAZOLE: SOLID-STATE PROPERTIES, DISSOLUTION, STABILITY, ANTIFUNGAL POTENTIAL, AND SOLUTION-MEDIATED PHASE TRANSFORMATION STUDIES

The physical form of drugs significantly influences their effectiveness, particularly for BCS Class II compounds. The interplay between crystal structure and formulation is critical in determining bioavailability. Crystal engineering has emerged as an efficient tool to increase the solid-state characteristics of APIs while preserving their intrinsic structures. This study focused on itraconazole (ITZ), a poorly water-soluble drug, developing pharmaceutical cocrystals via the solvent drop grinding technique using various coformers to enhance solubility, dissolution rate, and bioavailability. The ITZ cocrystals were evaluated for Fourier transform infrared (FTIR), Differential scanning calorimetry (DSC), and X-ray diffractometry (XRD) analyses and evaluated for solubility, dissolution, and stability. In-vitro antifungal activity was assessed and compared with pure ITZ. Among the formulations, cocrystals developed with glycine (GLY) and serine (SER) exhibited stable forms, while those with benzoic acid (BENZ), proline (PRO), and succinic acid (SU) showed solution-mediated phase transformations. Nonetheless, all cocrystals demonstrated enhanced in vitro antifungal activity. Furthermore, stability studies confirmed that the cocrystals retained their properties after 45 days of storage at 40°C and 75% RH. These findings highlight the potential of ITZ cocrystals as effective candidates for improving solubility, dissolution, and antifungal activity. This crystal engineering-based strategy offers a valuable pathway to address challenges associated with poorly water-soluble drugs, enhancing therapeutic efficacy and advancing drug delivery systems for BCS Class II compounds.