NUCLEAR-MAGNETIC-RESONANCE INVESTIGATIONS OF THE INCLUSION COMPLEXATION OF GLICLAZIDE WITH BETA-CYCLODEXTRIN

The formation of the gliclazide-beta-cyclodextrin (GL-beta-CD) inclusi on compound has been studied in the liquid state by phase solubility t echniques and by H-1 and C-13 NMR spectroscopy. From the initial strai ght portion of the solubility curve (B-S type), the value of the appar ent stability constant (K-C) was calculated as 1094 M(-1). The nuclear magnetic resonance studies confirm that GL yields a complex with beta -CD in aqueous medium, which is mainly due to the penetration of the a zabicyclooctyl group of GL into the cavity of beta-CD. The study of th e monodimensional nuclear Overhauser effect (NOE) of the H-3 proton of CD has shown that the tolyl group also interacts with CD, but to a le sser extent than the azabicyclooctyl moiety. Finally, the application of the continous variation technique confirmed the 1:2 drug:CD stoichi ometry of the complex.