Nuclear magnetic resonance and infrared spectroscopic analysis of nedocromil hydrates.

Abstract

Nedocromil sodium (NS), which is used in the treatment of reversible obstructive airway diseases, such as asthma, has been found to exist in the following solid phases: the heptahemihydrate, the trihydrate, a monohydrate, an amorphous phase, which contains variable amounts of water, and a recently discovered methanol + water (MW) solvate. Our aim was to apply 13C solid-state nuclear magnetic resonance (NMR) spectroscopy and solid-state Fourier transform infrared (FTIR) spectroscopy to the study of specific interactions in the various solid forms of NS. The 13C solid-state NMR and FTIR spectra of the various solid forms of NS were obtained and were related to the crystal structures of NS, the conformations of the nedocromil anion, and the interactions of the water molecules in these crystals. The 13C solid-state NMR spectrum is sensitive to the conformation of the nedocromil anion, while the solid-state FTIR spectrum is sensitive to interactions of water molecules in the solid state. In NS monohydrate, for which the crystal structure has not yet been solved, and in the amorphous phase, the information about the conformations of the nedocromil anion and the interactions of the water molecules are deduced from the 13C solid-state NMR spectra and solid-state FTIR spectra, respectively. 13C solid-state NMR spectroscopy and solid-state FTIR spectroscopy are shown to be powerful complementary tools for probing the chemical environment of molecules in the solid state, specifically the conformation of the nedocromil anion and the interactions of water-molecules, respectively.