Synthesis and Preliminary Characterization of Sulfamethazine-Theophylline Co-Crystal

Co-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 center dot center dot center dot H-N), and two intermolecular hydrogen bonds (O center dot center dot center dot H-N and N center dot center dot center dot H-N) keep the theophylline attached the dimer. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4042-4047, 2010