Multinuclear solid state NMR investigation of two polymorphic forms of Ciprofloxacin-saccharinate

Abstract

Two polymorphic forms of a novel pharmaceutical compound, ciprofloxacin-saccharinate (CIP-SAC), are analyzed using one dimensional (1D) and two dimensional (2D) ¹H nuclear magnetic resonance (NMR) at fast magic angle spinning (MAS). Additionally ¹⁵N spectroscopy and ¹H–¹³C correlation experiments were performed to complement our conclusions. The 1D ¹H NMR spectra of CIP and complexes reveal valuable information about the ionic bonding between ciprofloxacin and saccharine. Additionally, these spectra allow us to perform a clear characterization of each solid form, giving the number of molecules per unit cell in one of the polymorphs. From 2D ¹H–¹H spectra obtained through double quantum correlations we can arrive at important conclusions about the hydrogen bonding, conformation, and intra and inter-molecular interactions present in these compounds. Comparing and contrasting the ¹H–¹H correlation data obtained for both polymorphic forms and taking into account the single crystal structure data existing for the solid form CIP-SAC (II) was possible to extract some conclusions on the polymorph CIP-SAC (I) where no single crystal information is available. ¹H MAS NMR is shown to be an important tool in the field of polymorphism and for the characterization of multicomponent pharmaceutical compounds.