A crystal engineering study of selected sulfa drugs and trimethoprim
The objective was to prepare new solid phases, i.e. co-crystal forms, of two sulfa antibiotic drugs (sulfamethoxazole and sulfasalazine) with trimethoprim and fourteen potential co-formers with GRAS status. Trimethoprim was chosen for its synergistic effects with both sulfa drugs and the other co-formers were selected in an attempt to improve the physicochemical properties of the antibiotics. A variety of co-crystallization techniques, including solvent assisted grinding, slow evaporation, slurry method and solidification of the melt were used to obtain these results. From these methods, three new solid phases were successfully isolated for the sulfamethoxazole antibiotic, viz. sulfamethoxazole-benzoic anhydride (SMZ-BAN) co-crystal by the slurry method, amorphous sulfamethoxazole-trimethoprim (SMZ-TMP) form by solidification of the melt and amorphous sulfamethoxazole-oxalic acid (SMZ-OA) by slow evaporation. For the sulfasalazine antibiotic, co-crystallization experimentation produced, sulfasalazine-trimethoprim salt (SSZ-TMPs) by slow evaporation, sulfasalazine-trimethoprim co-crystal (SSZ-TMP) by solvent assisted grinding and sulfasalazine-nicotinamide co-crystal (SSZ-NC) by solidification of the melt. Of these six compounds subjected to single crystal X-ray analysis, only one of their structures was elucidated i.e. the salt, SSZ-TMPs. Different techniques that were used to assess the thermal behaviour of the products included hot stage microscopy, differential scanning calorimetry and thermogravimetric analysis. FTIR provided information on the purity of the compounds and the suggested host-guest interaction sites. X-ray powder diffraction supported the determination of the new phase comparative to the parent compounds. Finally dissolution testing was carried out for successful candidates with encouraging recommendations for future work.