Structural Features and Interactions of New Sulfamethazine Salt and Cocrystal

Abstract This study explored cocrystal/salt interactions through solid-state characterization and theoretical computation. A novel pharmaceutical salt and cocrystal of sulfamethazine (SMA), sulfamethazine-dichlofenac acid salt (SMA-DA), and sulfamethazine-piperazine cocrystal (SMA-PZ) were prepared through solvent-assisted grinding and solvent evaporation. The solid-state characterization included powder X-ray diffraction, single crystal X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy. Crystal structure analysis shows that SMA and DA create a 1:1 salt with proton transfer, and SMA and PZ create a 1: 0.5 cocrystal. The difference between salt and cocrystal is presented through solid-state characterization and density functional calculations, including Hirshfeld surface and molecular electrostatic potential surface.