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Preparation of ursolic acid–phospholipid complex by solvent-assisted grinding method to improve dissolution and oral bioavailability

Abstract To improve the aqueous solubility and the oral bioavailability of a poorly water-soluble biologically active pentacyclic triterpenoid, ursolic acid (UA), ursolic acid–phospholipid complex (UA–PC) was prepared using solvent-assisted grinding method which is green and simple. The phospholipid complex was characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), and transmission electron microscope (TEM), which confirmed the formation of the phospholipid complex. Specifically, compared with free UA, the formulation demonstrated over 276-fold higher aqueous solubility of UA and exhibited faster dissolution rate and higher cumulative dissolution percentages. Finally, the oral bioavailability of the prepared UA–PC was evaluated using Sprague-Dawley (SD) rats. Compared with free UA, the UA–PC exhibited considerable enhancement in the bioavailability with an increase in Cmax (183.80 vs 68.26 μg/l) and AUC 0–24 h (878.0 vs 212.1 μg·h/l), which was consistent with the in vitro results. This enhancement was attributed to the improvement of solubility and dissolution in vitro. Therefore, the method of solvent-assisted grinding appears to be an efficient approach for the preparation of UA–PC, and the prepared UA–PC showed a promising potential to overcome the limitation of poor oral bioavailability associated with low water solubility. Graphical Abstract