Nuclear magnetic resonance investigations of the inclusion complexation of gliclazide with beta-cyclodextrin.
The formation of the gliclazide-beta-cyclodextrin (GL-beta-CD) inclusion compound has been studied in the liquid state by phase solubility techniques and by 1H and 13C NMR spectroscopy. From the initial straight portion of the solubility curve (Bs type), the value of the apparent stability constant (Kc) 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 azabicyclooctyl group of GL into the cavity of beta-CD. The study of the monodimensional nuclear Overhauser effect (NOE) of the H3 proton of CD has shown that the tolyl group also interacts with CD, but to a lesser extent than the azabicyclooctyl moiety. Finally, the application of the continous variation technique confirmed the 1:2 drug:CD stoichiometry of the complex.
Moyano
J R
JR
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, Spain.
Arias-Blanco
M J
MJ
Gines
J M
JM
Rabasco
A M
AM
Pérez-Martínez
J I
JI
Mor
M
M
Giordano
F
F
D003505:Cyclodextrins / Q000737:chemistry*; D005907:Gliclazide / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D007004:Hypoglycemic Agents; D047392:beta-Cyclodextrins; D005907:Gliclazide; C031215:betadex