Multicomponent Crystal of Trimethoprim and Citric Acid: Solid State Characterization and Dissolution Rate Studies

Abstract

BACKGROUND: Trimethoprim is a broad-spectrum antimicrobial agent with low solubility in water which causes low bioavailability in the systemic circulation. AIM: This study aimed to increase the solubility and dissolution rate of trimethoprim by preparing multicomponent crystals of trimethoprim and citric acid. MATERIALS AND METHODS: Multicomponent crystals were prepared by the solvent evaporation method. Characterizations of multicomponent crystalline solid phase properties were carried out by powder X-ray diffraction (PXRD) analysis, differential scanning calorimetry (DSC), FT-IR spectroscopy, scanning electron microscopy (SEM). Solubility and dissolution rate tests were carried out in an aqueous medium. RESULTS: The PXRD characterization results showed a new X-ray diffraction pattern in the multicomponent crystal phase. DSC analysis showed the formation of a new endothermic peak. This indicates the formation of multicomponent crystal phase between trimethoprim and citric acid. The results of the SEM analysis indicate the formation of a new crystal habit. Solubility of multi-component crystal phase of trimethoprim increased seven times compared to intact trimethoprim. The dissolution of trimethoprim and multicomponent crystals in 0.1 N HCl medium at 60 min was 56.36% and 95.57% and the CO2-free distilled water medium was 43.03% and 88.26%, respectively. CONCLUSIONS: Based on the results of this study, it could be concluded that the novel multicomponent phase of trimethoprim crystals with citric acid successfully increases the solubility and dissolution rate of trimethoprim significantly.