A nuclear magnetic resonance study of the miconazole-β-cyclodextrin inclusion complex in an acidic medium:: determination of the structure and stability constants

Miconazole is a very sparingly water-soluble drug. Its solubility can be increased by the synergistic effect of both acids and cyclodextrins. The aim of this study is to understand how miconazole in its ionised form can be included in the beta -cyclodextrin cavity. Using H-1, C-13 and 2D-NMR spectroscopy, we could demonstrate that the most probable part included in the beta CD cavity is the dichlorobenzene cycle not directly linked to the asymmetric carbon (-O-CH2-dichlorobenzene). We could also show that in an acidic medium, miconazole and beta CD interact in the ratio of 1/1 and that the apparent stability constants of both enantiomers are relatively low, around 1000 and 1500 M-1 respectively.