Abstract
Inclusion complexes of an antifungal drug, itraconazole, with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) were prepared using a supercritical antisolvent (SAS) process. The optimum process condition was investigated in the temperature range of 35∼65°C and at pressures ranging from 83 to 140 bar. Mixed solvents of various compositions were used to dissolve itraconazole and HP-β-CD simultaneously. For a 3%(w/v) solution, the complexation efficiency of itraconazole with HP-β-CD was observed to increase with the pressure at a constant temperature. In order to evaluate the degree of complexation, the thermal behavior of solid microparticulate complexes was investigated using differential scanning calorimetry. The experimental results obtained for the solubility and dissolution rate in a buffer solution of pH 1.2 showed that the presence of cyclodextrin results in a significant increase of the solubility and dissolution rate of water-insoluble itraconazole. For the itraconazole/HP-β-CD inclusion complexes prepared in this study, about 80% of itraconazole was dissolved in the buffer solution. The present results suggest that the SAS process is a promising method for the preparation of cyclodextrin inclusion complex microparticles of water-insoluble drugs.
