Sulfamethoxazole salts: crystal structures, conformations and solubility

Sulfamethoxazole (SMZ) is a synthetic broad-spectrum antibiotic of biopharmaceutical classification system (BCS) class IV, with both low solubility and permeability, requiring probably higher drug doses in orally-administered formulations to promote an expected systemic absorption. To overcome such limitations and especially to increase its solubility, this study has a main purpose of the development of novel optimized crystalline forms of SMZ. Herein, two crystalline salts of SMZ (SMZBr and SMZNO(3)) have been synthesized from solution crystallization and characterized using X-ray (single and powder), spectroscopic (infrared, FT-IR) and thermal (DSC and TGA) techniques. Furthermore, a solubility study was performed in pure water and compared with the SMZCl salt and SMZ form I. It was observed that the SMZBr salt exhibits phase stability in water media and shows enhanced solubility compared to the SMZCl salt and SMZ form I. Additionally, a qualitative litmus paper test was employed to verify the volatiles released during the thermal drug degradation.