SOLUBILITY ENHANCEMENT OF VORICONAZOLE BY PHARMACEUTICAL CO-CRYSTALLIZATION WITH NICOTINIC ACID AND SUCCINIC ACID

Voriconazole (VCZ) is a poorly water-soluble antifungal drug whose limited aqueous solubility may restrict its dissolution and oral biopharmaceutical performance. The present study investigated pharmaceutical co-crystallization as a strategy to enhance the aqueous solubility and dissolution characteristics of VCZ. Co-crystals were prepared using nicotinic acid (NA) and succinic acid (SA) as pharmaceutically acceptable coformers at 1:1 and 1:2 drug-to-coformer ratios (w/w) by Liquid-Assisted Grinding (LAG) and Solvent Evaporation (SE) methods. Eight co-crystal formulations (T1–T8) were prepared and evaluated comparatively for saturation solubility and in vitro dissolution performance. The prepared systems were further characterized using appropriate analytical and solid-state characterization techniques to assess co-crystal formation. All co-crystal systems demonstrated improved aqueous solubility compared with pure VCZ (0.47 mg/mL). Among the investigated formulations, the VCZ–SA system prepared at a 1:2 w/w ratio by SE (T8) exhibited the highest solubility of 3.204 mg/mL, corresponding to an approximately 6.82-fold enhancement compared with pure VCZ. T8 also demonstrated superior dissolution performance, with 92.877% drug release at 60 min compared with 23.39% for pure VCZ. Formulation T8 exhibited the most favorable dissolution characteristics, with the lowest T50 and highest DE10, DE30, DE60 and RDR30 values. FTIR analysis confirmed that the characteristic functional groups of VCZ remained intact after co-crystallization, indicating the absence of any chemical degradation. The findings demonstrate that coformer selection, drug-to-coformer ratio, and preparation method substantially influence the solubility and dissolution behaviour of VCZ. The VCZ–SA co-crystal prepared by SE therefore represents a promising approach for enhancing the aqueous solubility and dissolution of VCZ.