Toward Novel Pseudo-Polymorphs of Nifedipine: Elucidation of a Slow Crystallization Process

The crystallization of nifedipine was studied by means of synchrotron-X-ray diffraction, single-crystal X-ray structural analysis, and Raman spectroscopy. The results of slow evaporation (24 h in minimum) using dimethyl sulfoxide (DMSO) are presented. Since fast crystallization processes (typically minutes) in different solvents always led to the final formation of the thermodynamically most stable α-polymorph of nifedipine, we observed a novel pseudo-polymorph due to slow crystallization from DMSO. The single-crystal X-ray structure of the solvated species nifedipine·DMSO (1:1) is reported for the first time. In addition, the crystallization process on surfaces was followed by means of light microscopy and environmental scanning electron microscopy (ESEM) coupled with energy-dispersive X-ray spectroscopy (EDS) analysis. Different diffractions pattern and Raman spectra were observed for crystals grown from stock solution and those obtained by drying the solution on soda lime silicate surfaces.