HIGH-FIELD NUCLEAR-MAGNETIC-RESONANCE TECHNIQUES FOR THE INVESTIGATION OF A BETA-CYCLODEXTRIN-INDOMETHACIN INCLUSION COMPLEX

The inclusion complex of indomethacin sodium salt in β‐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 β‐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. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company