Co-Amorphous Ursolic Acid-Quercetin Complex Improves Solubility and In Vivo Expectorant-Antitussive Activity.

This study investigated the formation of a co-amorphous complex between ursolic acid and quercetin as a chemically defined model system for improving the formulation performance of a poorly soluble triterpenoid acid. Co-amorphous systems were prepared by solvent evaporation and physical grinding at different mass ratios. The optimal formulations were identified and evaluated by water-solubility measurement, powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), and in vivo expectorant-antitussive assays. The solvent-derived system showed higher water solubility than the ground system. PXRD and FTIR results suggested that the solvent method more effectively promoted loss of crystallinity and probable intermolecular interactions, whereas the grinding method largely retained the crystalline features of ursolic acid. Both ursolic acid-quercetin formulations exhibited enhanced expectorant and antitussive activities compared with pure ursolic acid. Although quercetin may contribute intrinsic pharmacological activity, the overall improvements were broadly consistent with the altered physicochemical properties of the co-amorphous systems, which may facilitate ursolic acid delivery. As a secondary exploratory comparison, plant-derived triterpenoid-acid-rich and flavonoid-rich fractions from Eriobotrya japonica leaves were also co-processed; however, because these fractions were not compositionally characterized, their results were interpreted cautiously and were not used as the primary basis for mechanistic conclusions. Overall, the present study demonstrates that co-amorphous complexation of ursolic acid and quercetin is a promising strategy for improving the solubility-related properties and in vivo activity of a poorly soluble triterpenoid acid.