Abstract
The inclusion behavior of Itraconazole (Itra) with beta-cyclodextrin (beta-CD) and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated by using phase solubility and molecular mechanics techniques. The effects of pH and temperature on complex stabilit were also explored. The aqueous solubility of Itra was significantly enhanced as CD concentration increased. Itra tends to form 1: 3 complexes with beta-and HP-beta-CD at pH >= 4 and 1: 2 at pH 2. Thermodynamic parameters for Itra/HP-beta-CD show that the 1: 1 complex is driven by enthalpy but retarded by entropy changes. In contrast, the formation of 1: 2 and 1: 3 complexes is largely favored by entropy due to higher desolvation induced by total enclosure of Itra with two (or three) favorably interacting CD molecules. The inclusion mode of Itra/beta-CD complexes was proved by molecular mechanics technique, which provided a powerful means for understanding inclusion interactions and processes.