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

Int J Pharm. 1999 Mar 15;179(2):237-45. doi: 10.1016/s0378-5173(98)00393-7.

Abstract

The interaction of itraconazole, a triazole antifungal agent, with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) in water and 10% v/v propylene glycol/water solution at pH 2.0 was investigated by the solubility method and ultraviolet and 1H-nuclear magnetic resonance (NMR) spectroscopies. The solubility of itraconazole in water significantly increased as the concentrations of HP-beta-CyD were augmented, showing an AP type phase solubility diagram. The upward curvature closely corresponded to the simulation curve which was calculated on the basis of the 1:2 (guest:host) complexation model. The 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 weaker due to the competitive inclusion. The ultraviolet spectroscopic studies also 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 1H-NMR spectroscopic studies suggested that the triazole and triazolone moieties of itraconazole are involved in the 1:2 inclusion complexation.

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Antifungal Agents / administration & dosage*
  • Cyclodextrins / administration & dosage*
  • Drug Stability
  • Itraconazole / administration & dosage*
  • Itraconazole / chemistry
  • Propylene Glycol
  • Solubility
  • Solutions
  • beta-Cyclodextrins*

Substances

  • Antifungal Agents
  • Cyclodextrins
  • Solutions
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Itraconazole
  • Propylene Glycol