Crystal engineering to improve the dissolution behaviour of oleanolic acid

Abstract

In this work, we successfully synthesized five solid forms of oleanolic acid piperazine salt (OA–PIP) by liquid-assisted grinding and slurry methods. These solid materials were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared (FT-IR) spectroscopy, and the structure was 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 acceleration testing of the solid forms 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 behaviour. This result hints that form I of OA–PIP has the greatest potential for application.