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) (1)H nuclear magnetic resonance (NMR) at fast magic angle spinning (MAS). Additionally (15)N spectroscopy and (1)H-(13)C correlation experiments were performed to complement our conclusions. The 1D (1)H 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 (1)H-(1)H 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 (1)H-(1)H 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. (1)H MAS NMR is shown to be an important tool in the field of polymorphism and for the characterization of multicomponent pharmaceutical compounds.

Pharmaceutical salts of ciprofloxacin with dicarboxylic acids

“…For example, preparation and solubility profiles of CIP salts with carboxylic acids such as citric, tartaric, and malonic acids have previously been reported by Reddy et al (2011). Saccharinate of ciprofloxacin is found to be polymorphic, with two forms currently established (Romanuk et al, 2009(Romanuk et al, , 2010Garro Linck et al, 2011). It has also been shown that salt formation between dicarboxylic acids and CIP often leads to crystallization with multiple stoichiometries and hydration levels (Paluch et al, 2013).…”

Investigating Albendazole Desmotropes by Solid-State NMR Spectroscopy

“…Solid-state nuclear magnetic resonance (ssNMR) spectroscopy is one of the main techniques to investigate the solid-state molecular structure of an API. In order to obtain high resolution information at the molecular level, it is necessary to utilize ssNMR techniques with fast magic angle spinning (MAS). , By virtue of the recent technological and instrumental advancements in NMR, high-resolution one-dimensional (1D) and two-dimensional (2D) solid-state NMR techniques, particularly those based on 1 H-detection, are gaining considerable popularity nowadays and have recently been applied to a wide variety of systems. − In particular, the recent introduction of ultrafast MAS NMR probes that can achieve sample spinning rates up to 110 kHz makes it possible to obtain multidimensional high-resolution 1 H NMR spectra of organic solids, which facilitates structural and dynamic characterization of pharmaceutical systems at the atomic level. − A significant body of information can be retrieved from solid-state 1D 1 H NMR spectra and 2D 1 H/ 1 H single quantum–single quantum (SQ–SQ) experiments utilizing the finite-pulse radiofrequency-driven recoupling sequence (fp-RFDR) for dipolar recoupling under ultrafast MAS − and single quantum–double quantum (SQ–DQ) experiments. − The visualization of 1 H– 1 H interactions is particularly useful in small API molecules and pharmaceutical complexes, as it provides unique information on both intramolecular and intermolecular interactions, molecular packing, and hydrogen bonding. − In addition, the known examples about desmotropy have been investigated mainly with the aid of solid-state NMR and infrared spectroscopy …”

Structural Determination of a Novel Polymorph of Sulfathiazole–Oxalic Acid Complex in Powder Form by Solid-State NMR Spectroscopy on the Basis of Crystallographic Structure of Another Polymorph

“…30,31 Interaction sites in the complexes are identified by the pulse sequences of 2D 1 H− 13 C heteronuclear correlation (HETCOR) and 14 N− 1 H heteronuclear multiplequantum coherence (HMQC). 35 Sulfathiazole (STZ) is an antimicrobial agent used as a shortacting sulfa drug. The extreme polymorphism of STZ has been the subject of investigations in pharmaceutical sciences for over 70 years.…”