Ciprofloxacin salts with benzoic acid derivatives: structural aspects, solid-state properties and solubility performance

In this work, three new pharmaceutical hydrated salts of ciprofloxacin with selected derivatives of benzoic acid, namely 4-hydroxybenzoic acid, 4-aminobenzoic acid and gallic acid, were obtained and systematically investigated by several solid-state analytical techniques. In situ Raman spectroscopy was applied to elucidate the alternative pathways of the solid forms' formation under mechanochemical conditions. Crystal structure analysis and a CSD survey allowed us to establish a distinct supramolecular motif formed by infinite columnar stacks of ciprofloxacin dimers arranged in the "head-to-tail" manner. An alternative "head-to-head" packing arrangement was only observed in the crystal of the hydrated ciprofloxacin salt with 4-aminobenzoic acid. In addition, the pH-solubility behavior of the solid forms was thoroughly investigated. Furthermore, a distinct structure-property relationship between the specific features of the supramolecular organization of the hydrated salts and their solubility was observed and discussed. In this work, three new pharmaceutical hydrated salts of ciprofloxacin with selected derivatives of benzoic acid were obtained and systematically investigated by several solid-state analytical techniques.