Crystal Engineering Improve the Dissolution Behavior of Oleanolic Acid

Abstract

In this work, we successfully synthesized five polymorphs of oleanolic acid piperazine salt (OA-PIP) by liquid-assisted grinding and slurry methods. Those solid materials were characterized by powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR) Spectroscopy, and structure determined by single crystal X-ray diffraction (SXRD). Form I and form IV are anhydrous polymorphs, form II is a hydrate, form III is an amorphous form and form V is an ethanol solvate. Besides, the accelerated stability of the polymorphs was explored. During stability studies, Form III gradually converted to the crystalline state, indicating its physical instability. Form I showed good stability, the best dissolution rate and excellent dissolution behavior. This result hints that form I of OA-PIP has the greatest potential for application.