Crystal characterization and transformation of the forms I and II of anticoagulant drug rivaroxaban

Abstract

The crystal forms I and II of rivaroxaban were characterized by powder X‐ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Powder dissolution testing was carried out at 310.15 K in the dissolution media at pH = 1.0 and pH = 6.8, respectively. The solution‐mediated phase transformation from form II to form I was investigated under different temperature, slurry density and stirring speed, respectively, by use of the FTIR spectroscopy. The results showed that, the two forms were monotropically‐related, and in the both dissolution media the concentration of form II was obviously higher than that of form I at the same time which demonstrated that form II was the metastable form. Among the evaluated solid‐state kinetic models the Prout‐Tompkins and Avrami‐Erofeev (n = 3) equations gave a satisfactory correlation of the phase transformation process from form II to form I. The activation energy of phase transformation was calculated as 19.151 kJ·mol−1 by means of Arrhenius analysis. In addition, the phase transformation rate increased with increasing temperature, slurry density and stirring speed.