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