High-field nuclear magnetic resonance techniques for the investigation of a beta-cyclodextrin:indomethacin inclusion complex.

The inclusion complex of indomethacin sodium salt in beta-cyclodextrin has been studied by proton NMR at high magnetic field. The continuous variation technique was used to evidence the formation of a soluble 1:1 complex in aqueous solution at physiological pH. The effective association constant was determined by the Benesi-Hildebrand procedure to be 760 M-1 at 303 K. This technique requires NMR measurements in the presence of a very large excess of one of the complex components and, since both beta-cyclodextrin and the sodium salt of indomethacin are sparingly soluble in water, NMR spectrometers operating at very high magnetic fields were used. Besides the effective association constant, the Benesi-Hildebrand approach allows a precise determination of all NMR parameters of the pure inclusion complex which may be used for a complete analysis of the geometry of this complex in solution.