Crystal structures of norfloxacin hydrates

Abstract

Two novel hydrate forms of norfloxacin (NF) were serendipitously obtained during cocrystallization with eugenol. NF 1.25 hydrate and 1.125 hydrate are isomorphous crystal structures in the P2₁/c space group, each with two symmetry-independent drug molecules, two full water molecules, and a third water of 0.5 and 0.25 partial occupancy, respectively. Water promoted proton transfer results in a shift from neutral to ionic hydrogen bonding between norfloxacin molecules in hydrate structures. The presence of eugenol additive gave novel NF hydrates of lower water stoichiometry, whereas crystallization in its absence gave the known NF dihydrate.