A thermodynamic relationship and phase transition study involving two polymorphs of sulfamethoxazole: form I vs. form II†
Abstract
Sulfamethoxazole (SMZ) is a synthetic, broad-spectrum antibiotic presenting five known polymorphic forms. Herein, the SMZ polymorph I (SMZI), which is the preconised form for SMZ pharmaceutical oral solid formulations, and SMZ polymorph II (SMZII) were grown and systematically characterized by powder X-ray diffraction, infrared spectroscopy, and differential scanning calorimetry. The thermal behaviour of the SMZI and SMZII samples was studied by cyclic differential scanning calorimetry experiments, revealing, for the first time, the exothermic event attributed to the SMZII crystallization from the SMZ molten material. It was also demonstrated that the SMZII polymorph can be solid-state transformed to the SMZI polymorph by milling. The solubilities of SMZI and SMZII forms in acetonitrile media were found to be equivalent, which can be attributed to the SMZII → SMZI phase transition that occurs during the equilibrium solubility test. A proposed phase transition mechanism for the SMZI–SMZII enantiotropic polymorph pair is presented here for the first time.