Abstract
Purpose. Nedocromil sodium (NS), which is used in the treatment ofreversible obstructive airway diseases, such as asthma, has been foundto exist in the following solid phases: the heptahemihydrate, thetrihydrate, a monohydrate, an amorphous phase, which contains variableamounts of water, and a recently discovered methanol + water (MW)solvate. Our aim was to apply 13C solid-state nuclear magneticresonance (NMR) spectroscopy and solid-state Fourier transform infrared(FTIR) spectroscopy to the study of specific interactions in the varioussolid forms of NS.
Methods. The 13 solid-state NMR and FTIR spectra of the varioussolid forms of NS were obtained and were related to the crystalstructures of NS, the conformations of the nedocromil anion, and theinteractions of the water molecules in these crystals.
Results. The 13C solid-state NMR spectrum is sensitive to theconformation of the nedocromil anion, while the solid-state FTIR spectrumis sensitive to interactions of water molecules in the solid state. In NSmonohydrate, for which the crystal structure has not yet been solved,and in the amorphous phase, the information about the conformationsof the nedocromil anion and the interactions of the water moleculesare deduced from the 13C solid-state NMR spectra and solid-state FTIRspectra, respectively.
Conclusions. 13C solid-state NMR spectroscopy and solid-state FTIRspectroscopy are shown to be powerful complementary tools forprobing the chemical environment of molecules in the solid state,specifically the conformation of the nedocromil anion and the interactions ofwater-molecules, respectively.
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Chen, L.R., Padden, B.E., Vippagunta, S.R. et al. Nuclear Magnetic Resonance and Infrared Spectroscopic Analysis of Nedocromil Hydrates. Pharm Res 17, 619–624 (2000). https://doi.org/10.1023/A:1007533419711
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DOI: https://doi.org/10.1023/A:1007533419711