Phase solubility and inclusion complex of itraconazole with β-cyclodextrin using supercritical carbon dioxide

Phase-solubility techniques were used to assess the formation of inclusion complex between itraconazole and β-cyclodextrin. The stability constant and free energies of transfer of itraconazole from aqueous solution to the cavity of β-cyclodextrin were calculated. Itraconazole solubility in supercritical carbon dioxide (SC CO₂) was measured at different temperatures and pressures. Drug formulations of itraconazole were prepared by complexation of the drug into β-cyclodextrin using SC CO₂. Effects of temperature and pressure on inclusion yield of the prepared complexes were studied. The solvent-free inclusion complexes obtained from this method were characterized by UV spectroscopy, differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy and compared to those obtained from physical mixing and coprecipitation methods. Results showed that β-cyclodextrin significantly improved solubility of itraconazole in aqueous solutions. The free energies of transfer of itraconazole from aqueous solution to the cavity of β-cyclodextrin increased negatively with increasing β-cyclodextrin concentration. Higher inclusion yields were obtained in the SC CO₂ method compared to physical mixing and coprecipitation methods. Both temperature and pressure had significant effects on itraconazole solubility in SC CO₂ and the inclusion yield of the complex prepared by SC CO₂ method.