Origin of phase relative stability and phase transformation in an S-ibuprofen–nicotinamide cocrystal

The crystal structure of the metastable form of S-ibuprofen–nicotinamide cocrystals, C13H18O2·C6H6N2O, was solved from powder X-ray diffraction. This form was obtained by melting a molar mixture of S-ibuprofen and nicotinamide at 100 °C, and then cooling. The high-resolution powder X-ray diffraction pattern of this new phase was recorded at room temperature using synchrotron radiation at SOLEIL Synchrotron (France). A hypothetical structure was obtained from the Monte-Carlo simulated annealing method and confirmed by Rietveld refinement. The symmetry is monoclinic (space group P21, No. 4) and the unit cell contains four molecules, two of nicotinamide and two of S-ibuprofen. Density functional theory (DFT) energy minimization simulation was performed in order to locate the H atoms. The determination of the crystallographic structure of this metastable form allowed an explanation of the main mechanisms at the origin of the relative stability of the two forms of the S-ibuprofen–nicotinamide cocrystals. This also made it possible to explain the transition mechanism between the two forms with temperature.