Characterization of itraconazole/2-hydroxypropyl-beta-cyclodextrin inclusion complex in aqueous propylene glycol solution.
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.
Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oehonmachi, Kumamoto 862-0973, Japan.
K
K
Miyake
T
T
Irie
H
H
Arima
F
F
Hirayama
K
K
Uekama
M
M
Hirano
Y
Y
Okamaoto
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000935:Antifungal Agents / Q000008:administration & dosage*; D003505:Cyclodextrins / Q000008:administration & dosage*; D004355:Drug Stability; D017964:Itraconazole / Q000008:administration & dosage* / Q000737:chemistry; D019946:Propylene Glycol; D012995:Solubility; D012996:Solutions; D047392:beta-Cyclodextrins
D000935:Antifungal Agents; D003505:Cyclodextrins; D012996:Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D017964:Itraconazole; D019946:Propylene Glycol