Concurrent modulation of solubility and antibacterial activity in trimethoprim-meloxicam drug-drug salt

A novel drug-drug salt composed of trimethoprim (TMP), a broad-spectrum antibiotic, and meloxicam (Mobic), a non-steroidal anti-inflammatory drug, was synthesized and structurally characterized. The salt was analyzed using single-crystal and powder X-ray diffraction, thermal analysis, and Fourier-transform infrared spectroscopy. Structural analysis revealed a 1:1 stoichiometric composition comprising two TMP + cations and two MLX − anions in the asymmetric unit, stabilized by N H···N and N H···O hydrogen bonds, forming a tetrameric assembly within the triclinic space group P -1. Equilibrium solubility studies in pure water revealed that the salt markedly reduced TMP solubility by 98.0 % while increasing MLX solubility by 4.4-fold, demonstrating that can effectively modulate the dissolution profiles of both active pharmaceutical ingredients (APIs) simultaneously. Moreover, antimicrobial evaluation demonstrated enhanced antibacterial activity of the salt against Escherichia coli at concentrations of 0.7 and 0.8 mmol/L (P < 0.05) compared to the individual components. These results underscore the potential of drug-drug salts to fine-tune the physicochemical and biological properties of APIs, providing a promising strategy for the development of optimized combination therapies.