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, C 13 H 18 O 2 ·C 6 H 6 N 2 O, 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 P 2 1 , 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.