In Situ Monitoring and Modeling of the Solution-Mediated Polymorphic Transformation of Rifampicin: From Form II to Form I

In this article, the solution-mediated polymorphic transformation of rifampicin was investigated and simulated in 3 solvents at 30°C. The solid-state form I and form II of rifampicin was characterized by powder X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, Raman spectroscopy, and Fourier transform infrared spectroscopy (FTIR). To explore the relative stability, solubility data of form I and form II of rifampicin in butan-1-ol were determined using a dynamical method. In addition, Raman spectroscopy and focused beam reflectance measurement were used to in situ monitor the transformation of rifampicin from form II to form I. The liquid state concentration of rifampicin was measured by UV spectroscopic method. To investigate the effect of solvent on transformation, the transformation experiments were carried out in 3 solvents. Furthermore, a mathematical model was built to describe the kinetics of dissolution, nucleation, and growth processes during transformation by using experimental data. By combination of experimental and simulation results, it was found that the transformation process of rifampicin is controlled by dissolution of form II in heptane, whereas the transformation in hexane and octane was firstly controlled by dissolution of solid-state form and then controlled by growth of form I.