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 C_max (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

Keywords:

• Ursolic acid
• phospholipid complex
• solvent-assisted grinding
• oral bioavailability
• pharmacokinetics

Acknowledgements

The authors appreciated the Analytical department of Shenyang Pharmaceutical University for kindly support. The authors are also very grateful to Animal Center of Shenyang Pharmaceutical University for providing healthy male SD rats.

Disclosure statement

No potential conflict of interest was reported by the authors.