1 Section of Chemistry, The Faculty of Engineering and Science, Aalborg University, VBN2 Supramolekular Chemistry, The Faculty of Engineering and Science, Aalborg University, VBN3 Department of Chemistry and Bioscience, The Faculty of Engineering and Science, Aalborg University, VBN4 The Faculty of Engineering and Science, Aalborg University, VBN5 Department of Physics, Chemistry and Pharmacy, University of Southern Denmark
The aim of this work was to assess the potential of β-cyclodextrin (β-CD)-dextran polymers for drug delivery, in terms of molecular mass, the complexation reaction mechanism using a model drug, and solubilization efficiency for examples of poorly soluble model drugs. For this purpose size analysis of different β-CD-dextrans was carried out by both size exclusion chromatography (SEC) and flow field-flow fractionation (FFF). All investigated polymers were of appropriate sizes for potential parenteral administration. Mass/mass percentage ratio between β-CD units and dextran backbones where measured by both NMR and isothermal titration calorimetry. Moreover, thermodynamic parameters of the complexation reaction between β-CD units and drug molecules in terms of molar enthalpy of complexation, equilibrium constant, and stability of the β-CD units/drug molecules complexes were also measured. For evaluation of solubilization efficiencies, phase-solubility diagrams where made employing two poorly soluble model drugs, one dissociating (ibuprofen, IBP) and one pH independent (hydrocortisone, HC). Thermodynamic results demonstrated that the presence of the dextran-back bone structure improves complexation efficiency in terms of higher stability of the β-CD/IBP complex, in comparison to native β-cyclodextrin and solubility studies showed their superior solubilizing properties.
International Journal of Pharmaceutics, 2014, Vol 468, Issue 1-2, p. 258-263