Complexation study of midazolam hydrochloride with beta-cyclodextrin: NMR spectroscopic study in solution.

(1)H NMR spectroscopic study of midazolam hydrochloride (MDL), beta-cyclodextrin (beta-CD) and their mixtures confirmed the formation of beta-CD-MDL inclusion complex in aqueous solution. The stoichiometry of the complexes was determined by Scott's method to be 1:1, and the association constant (K(a)) was calculated to be 108 M(-1). It was confirmed on the basis of 2D ROESY spectral data that only a fluorine-substituted aromatic ring acted as guest in complexation. Most of the aromatic signals of MDL exhibited induced shift changes as well as splitting, in the presence of beta-CD, indicating chiral differentiation of MDL by beta-CD. Copyright (c) 2008 John Wiley & Sons, Ltd.