Synthesis, Characterization, and Properties of Rivaroxaban New Crystalline Forms

Abstract

In this paper, two new Rivaroxaban crystalline forms are reported and characterized by the single‐crystal X‐ray diffraction (SXRD), powder X‐ray diffraction (PXRD), thermogravimetric analysis, and differential scanning calorimetry (TGA/DSC), which are synthesized with formic acid and acetic acid, named as forms F and G, respectively. The intermolecular forces for forms F and G are analyzed by Hirshfeld surface analysis method, showing that the force of O···H is significantly stronger than that of H···H. Furthermore, the stability, solubility, and bioavailability of the two crystal forms are also studied. The clinical experiments show that form F is more effective than other reported crystal forms in inhibiting the activity of thrombin and thrombosis, which is expected to replace the marketed crystalline forms in clinical application.