Structural origin of physicochemical properties differences upon dehydration and polymorphic transformation of ciprofloxacin hydrochloride revealed by structure determination from powder X-ray diffraction data

Abstract

Ciprofloxacin hydrochloride (CIP) is a common fluoroquinolone antibiotic agent, and in the marketed product the compound exists as the hydrate phase (1.43 hydrate). Upon heating, the stable hydrate phase dehydrates and converts to a new anhydrous form 1 (AH1). Further heating results in a phase transformation that gives another new anhydrous form 2 (AH2). The crystal structures of CIP 1.43 hydrate and AH2 were solved from single crystal X-ray structure analysis. However, the single crystal of CIP AH1 could not be obtained, thus the crystal structure of CIP AH1 was determined directly from powder X-ray diffraction data using synchrotron technique. The crystal structure of AH1 is partly related to the hydrate as they both show similar one-dimensional (1D) chain and two-dimensional sheet structure. In the AH2, it is only the 1D chain that is retained after phase transformation. The mechanism of dehydration and the phase transformation is determined by correlating structural differences of AH1 and AH2. Each crystalline phase of CIP shows different physical stability, dissolution rate, and colour which can be derived from structural difference among the phases.