Nuclear magnetic resonance and infrared spectroscopic analysis of nedocromil hydrates

Purpose. Nedocromil sodium (NS), which is used in the treatment of reversib le obstructive airway diseases, such as asthma, has been found to exist in the following solid phases: the heptahemihydrate, the trihydrate, a monohyd rate, an amorphous phase, which contains variable amounts of water, and a r ecently discovered methanol + water(MW) solvate. Our aim was to apply C-13 solid-state nuclear magnetic resonance (NMR) spectroscopy and solid-state F ourier transform infrared (FTIR) spectroscopy to the study of specific inte ractions in the various solid forms of NS. Methods. The C-13 solid-state NMR and FTIR spectra of the: various solid fo rms of NS were obtained and were related to the crystal structures of NS, t he conformations of the nedocromil anion, and the interactions of the water molecules in these crystals. Results. The C-13 solid-start: NMR spectrum is sensitive to the conformatio n 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, acid in the amorph ous phase, the information about the conformations of the nedocromil anion and the interactions of the water molecules are deduced from the C-13 solid -state NMR spectra and solid-state FTIR spectra, respectively. Conclusions. C-13 solid-state NMR spectroscopy and solid-state FTIR spectro scopy 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, respectiv ely.