Characterization of itraconazole/2-hydroxypropyl-beta-cyclodextrin inclusion complex in aqueous propylene glycol solution

The interaction of itraconazole, a triazole antifungal agent, with 2-hydrox ypropyl-beta-cyclodextrin (HP-beta-CyD) in water and 10% v/v propylene glyc ol/water solution at pH 2.0 was investigated by the solubility method and u ltraviolet and H-1-nuclear magnetic resonance (NMR) spectroscopies. The sol ubility of itraconazole in water significantly increased as the concentrati ons of HP-beta-CyD were augmented, showing an A, type phase solubility diag ram. The upward curvature closely corresponded to the simulation curve whic h was calculated on the basis of the 1:2 (guest:host) complexation model. T he 1:2 complex was formed even in the presence of 10% v/v propylene glycol, although the co-solvent system made the interaction with HP-beta-CyD weake r due to the competitive inclusion. The ultraviolet spectroscopic studies a lso supported the 1:2 complex formation of itraconazole with HP-beta-CyD in 10% v/v propylene glycol/water solution at pH 2.0. The H-1-NMR spectroscop ic studies suggested that the triazole and triazolone moieties of itraconaz ole are involved in the 1:2 inclusion complexation. (C) 1999 Elsevier Scien ce B.V. All rights reserved.