Complex formation of chlorhexidine gluconate with hydroxypropyl-β-cyclodextrin (HPβCD) by proton nuclear magnetic resonance spectroscopy ((1)H NMR).

The complex formation of chlorhexidine digluconate (CHX-G(2)) with hydroxypropyl-β-cyclodextrin (HPβCD) was studied using NMR spectroscopy. The results revealed that this surfactant agent shows an monomer/aggregate equilibrium, which is dependent on the concentration of this drug. This equilibrium can be modified by the presence of HPβCD, which reduces the aggregation of the CHX-G(2) molecules. An inclusion process of the CHX-G(2) aromatic residue within the cyclodextrin cavity was confirmed by 2D ROESY spectroscopy. (1)H NMR titration studies of CHX-G(2) with HPβCD in D(2)O confirmed the formation of higher order complexes between CHX-G(2) and HPβCD. Moreover, the addition of HPβCD into CHX-G(2) solutions forms insoluble aggregates. Such insoluble aggregates may result in the stacking of CHX-G(2) molecules on the surface of the CHX-G(2):HPβCD complexes.