Preparation, Characterization, and Antioxidant Capacity of Xanthone-Urea Complex

Xanthones are a group of polyphenolic compounds widely known to have antitumor, anti-inflammatory, antibacterial, antifungal, antiviral, and antioxidant properties. To fully utilize their therapeutic potential, this study aimed to enhance the solubility of a poorly soluble xanthone by preparing a 1:1 molar ratio of xanthone-urea complex utilizing a cogrinding method via a vibration rod mill. DSC analysis revealed the disappearance of the characteristic endothermic peaks of xanthone (177 °C) and urea (136 °C) in the ground mixture (GM), along with the appearance of a new endothermic peak at 185 °C, indicating potential complexation. Additionally, new peaks were observed in the PXRD patterns of the GM at 9.1°, 12.0°, 14.0°, 18.6°, 19.6°, and 24.6°, suggesting structural changes that were also observed in SEM morphology. FTIR spectroscopy revealed significant shifts in the -NH and C=O peaks of xanthone and urea, as well as the disappearance of a -CN peak. Altered diffusion coefficients for both xanthone and urea were measured using DOSY-NMR, accompanied by notable improvements in solubility and dissolution profiles. The GM exhibited nearly a 2-fold increase in solubility, reaching 88.08 ± 1.25 µg/mL at 24 h and 90.97 ± 0.98 µg/mL at 72 h, alongside a 2-fold and 5-fold increase in dissolution at 0.21 µg/mL and 0.51 µg/mL for the physical mixture (PM) and GM, respectively. Furthermore, an enhanced antioxidant capacity was observed, as demonstrated in the calculated Trolox equivalent (TE) value, which increased from 1.48 ± 1.12 for xanthone alone to 1.65 ± 1.03 in the xanthone-urea complex. These findings confirm the successful complexation of xanthone and urea in a 1:1 molar ratio.