Three new orbifloxacin multicomponent crystal forms towards pharmaceutical improvement†

Abstract

Orbifloxacin (ORBI) is a third-generation synthetic fluoroquinolone used as an antimicrobial veterinary drug for the treatment of gastrointestinal and respiratory infections. Structural information about this drug is restricted to a hemihydrate containing ORBI as a zwitterion, which is the crystal form expected to be present in veterinary solid oral formations. Since the major problem with the ORBI hemihydrate form is its poor solubility and structure conservation upon dehydration, leading to uncontrollable water contents in the active pharmaceutical ingredient (API), we present here for the first time the crystal structures of three ORBI multicomponent crystal forms including two salt solvates and one cocrystal salt solvate: a hydrochloride salt monohydrate (1), a nitrate salt monohydrate (2) and a phosphoric acid hemi-cocrystal of the dihydrogen phosphate salt monohydrate (3). The latter form presents a very interesting multicomponent crystal feature having phosphate species either as a counter-ion or a neutral coformer. Pure crystalline samples of 1–3 were obtained and characterised by powder X-ray diffraction, infrared spectroscopy, thermogravimetry and differential thermal analyses. We have provided here a full analytical dataset for three new multicomponent solid forms of orbifloxacin, which may improve drug solubility and mitigate the possible drawback of inconsistent water load inherent to its hydrated free-base form.