2D homonuclear and heteronuclear correlation NMR experiments in solid state applied to a new pharmaceutical compound.

GARRO LINCK YAMILA; CHATTAH ANA KARINA; ROMAÑUK CAROLINA BEATRIZ; OLIVERA MARIA EUGENIA; MANZO RUBEN HILARIO; GRAF ROBERT; MONTI GUSTAVO; SPIESS HANS

Gotemburgo

Congreso; EUROMAR 2009; 2009

EUROMAR 2009

Ciprofloxacin (CIP) is a widely prescribed broad-spectrum oral fluoroquinolone antibiotic. Low solubility and bitter taste are unfavorable properties associated with most fluoroquinolones that limit their formulation. Saccharine (SAC) derivatives, either as salts or co-crystals, show an improved solubility behavior and better taste. Advanced solid state nuclear magnetic resonance (NMR) techniques have been used to study a new pharmaceutical compound, the ciprofloxacin saccharinate, CIP-SAC. This compound has been previously reported and fully characterized with a variety of solid state techniques (IR, DSC, XRD and 13C CP-MAS NMR). [Romañuk et al. J. Pharm. Sci. DOI: 10.1002/jps.2168] This saccharinate evidences polymorphism presenting two well distinguished solid forms, CIP-SAC (I) and (II). In this work we performed 2D 13C-1H heteronuclear correlation experiments (REPT-HSQC and HETCOR) which allowed the complete assignment of the resolved 1H solid state spectrum. [Kay Saalwächter, Robert Graf and Hans W. Spiess. J. Mag. Reson. 140, 471-476 (1999) and van Rossum et al. J. Mag. Reson. 124, 516–519 (1997)] These data were complemented with double quantum MAS experiments (BABA pulse sequence [M. Feike, D. E. Demco, R. Graf, J. Gottwald, S. Hafner, and H. W. Spiess. J. Mag. Reson. A 122, 214-221 (1996)]) to identify 1H-1H connectivities, hydrogen bonds and dipolar proximities. The zwitterionic character of ciprofloxacin and its derivative was identified. Further information about inter and intra molecular interactions in both solid forms of the new saccharinate was obtained. Differences and similarities in the structures of the different solid forms have also been established and supported with single crystal XR diffraction data obtained for CIP-SAC (II).