INVESTIGADORES
OLIVERA Maria Eugenia
congresos y reuniones científicas
Título:
2D homonuclear and heteronuclear correlation NMR experiments in solid state applied to a new pharmaceutical compound
Autor/es:
GARRO LINCK Y; CHATTAH AK; ROMAÑUK C; OLIVERA M.E; MANZO RH; GRAF R; MONTI GA; SPIESS HW
Lugar:
Gotemburgo, Suecia
Reunión:
Congreso; EUROMAR 2009; 2009
Resumen:
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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, 516519 (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).