From a binary salt to salt co-crystals of antibacterial agent lomefloxacin with improved solubility and bioavailability

Abstract

The cocrystallization of lomefloxacin (Lf) with barbituric acid (HBA) and/or isophthalic acid (H2ip) leads to novel binary and ternary saltsviahydrogen-bonding recognition. X-ray single-crystal diffraction analyses show that zwitterionic lomefloxacin can adjust itself to fulfill a different supramolecular array in either binary salts or ternary salt co-crystals, formulated as [HLf]·[Hip]·H2O (1), [HLf]·[BA]·[HBA]·H2O (2) and [HLf]·[BA]·[H2ip]·CH3OH·H2O (3). These pharmaceutical agents present uniform charge-assisted hydrogen-bonding networks between HLf cations and acidic coformers with the lattice capturing water molecules. Structural comparison of (2) and (3) indicated that a delicate balance of geometries and hydrogen-bonding partners is required for stacking to favor the formation of ternary salt co-crystals. Cocrystallization was able to overcome the water insolubility of lomefloxacin. Both the salt co-crystals display enhanced solubility and better pharmaceutical applicability.