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.