Sparfloxacin Multicomponent Crystals: Targeting the Solubility of Problematic Antibiotics

Abstract

The design of novel pharmaceutical multicomponent crystal forms has been reported as an efficient approach to tailor their physicochemical properties, including solubility. Sparfloxacin is a fluoroquinolone antibiotic widely used mainly in respiratory tract infections, but its safety profile is controversial due to photosensitivity reactions, and therefore the development of alternative forms that may contribute to the intake of lower dosages is desirable. Herein we report five novel molecular salts of sparfloxacin with generally regarded as safe coformers. All of the compounds present the typical S11(6) intramolecular synthon in SPAR molecules, and a direct interaction between SPAR+ and the anionic coformers is also verified. Only salts 2 and 5 present a C11(8) chain due to the direct interaction of SPAR molecules via N–HNH2,SPAR···OCOOH,SPAR. The new forms have been fully characterized, presenting adequate RH and temperature stability; more importantly, they are more soluble in water than sparfloxacin itself. The observed improvement in the physicochemical properties, in particular the 1 order higher aqueous solubility of the citrate salt, may contribute positively to obtain a better safety profile of the drug, as lower dosages may be possible.