Solubilization of ibuprofen with β-cyclodextrin derivatives: Energetic and structural studies

The aim of this work was to investigate the complexation of ibuprofen as model drug with various beta-cyclodextrins (native beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin with two different molar degrees of substitution, and methyl-beta-cyclodextrin). Solutions of the commercially available beta-cyclodextrins were prepared in phosphate buffer (73 mM). The pH value was adjusted to 7.4 and the solutions were isotonized with NaCl. A solution of ibuprofen was prepared in the same way. A thermal activity monitor was used for isothermal titration calorimetry (ITC). H-1 NMR analysis was employed to investigate the structures of the complexes. ITC analysis showed that each type of beta-cyclodextrin had its characteristic values of both enthalpy and mass equilibrium constant for the complexation processes with the drug molecules. H-1 NMR spectroscopy of the complexes showed through significant differences in chemical shifts that the physical interaction between the cyclodextrins and ibuprofen molecules were also different, probably due to different three-dimensional arrangements of ibuprofen in the cyclodextrin cavity, induced by the different substituents bonded to the glucose rings. These differences were connected to the thermodynamic parameters of the complexes. (C) 2011 Elsevier B.V. All rights reserved.