Drug–Drug Binary Solids of Nitrofurantoin and Trimethoprim: Crystal Engineering and Pharmaceutical Properties

With the aim of developing multidrug
solids through a tuned crystal
engineering approach, we have selected two antiurinary infective drugs,
namely, nitrofurantoin (NF) and trimethoprim (TMP) and isolated eight
binary drug–drug solid solvates along with a nonsolvated cocrystal.
Crystal structure analyses were performed for eight of these solids
and rationalized in terms of known supramolecular synthons formed
by pyrimidine, imide, and amine functionalities. Notably, the TMP–NF
anhydrous cocrystal and its ionic cocrystal hydrate exhibit enhanced
equilibrium solubilities compared to pure NF or the simple NF hydrate.
Furthermore, the ionic cocrystal hydrate exhibits greater antibacterial
activity against the Gram-negative bacteria, E. coli, compared to the parent TMP and NF at the lowest concentration of
3.9 μg/mL. This study indicates initial pathways using the cocrystal
methodology that would help to eventually arrive at an antiurinary
cocrystal with optimal properties.