Synthesis and Preliminary Characterization of Sulfamethazine-Theophylline Co-Crystal

ABSTRACTCo-crystals containing active pharmaceutical ingredients (APIs) represent a new type of pharmaceutical materials. In this work, sulfamethazine (STH) and theophylline (TP) were employed as the co-crystal formers. Neat cogrinding, solvent-drop cogrinding and slow evaporation were applied to synthesize the sulfamethazine-theophylline co-crystal (hereafter STH-TP co-crystal). The co-crystalline phase was characterized by DSC, TGA, Raman, PXRD, and dynamic vapor sorption (DVS) techniques. The STH-TP co-crystal structure was determined from single crystal X-ray diffraction data. The results show that, the STH-TP co-crystal, obtained in a 2:1 molar ratio of sulfamethazine and theophylline only by slow evaporation, possesses unique thermal, spectroscopic, and X-ray diffraction properties. Besides, in the STH-TP co-crystal, the sulfamethazine molecules form a dimer through the intermolecular hydrogen bonding (O ⋯ H — N), and two intermolecular hydrogen bonds (O ⋯ H — N and N ⋯ H — N) keep the theophylline attached the dimer. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4042–4047, 2010