Influence of the Cosolvent Composition on the Physical Properties of Itraconazole Solid Dispersion Prepared by Spray Drying

OBJECTIVE To investigate the influence of cosolvent compositiondifferent volume ratio of dichloromethane (DCM) and ethanol (EtOH) on the physical properties of itraconazole (ITRA) solid dispersion prepared by spray drying.METHODS The equilibrium solubility of ITRA in DCM and EtOH mixtures of different ratios at room temperature was measured using HPLC method. Four different solvent compositions including DCM:EtOH (100:0, 90:10, 70:30, 50:50) were selected to prepare spray-dried solid dispersion with VA64 PVP as carrier. The spray-dried powders were characterized using scanning electron microscopy, differential scanning calorimetry(DSC), contact angle goniometer and in vitro dissolution study. The physical stability of the samples was accessed with DSC by storing the samples at 90℃ for 48, 96 and 192 h. RESULTS The solubility of ITRA was highly dependent on the composition of cosolvent, and the solubility of ITRA in DCM and EtOH mixtures of different ratios was significantly different. ITRA formulations processed with 4 different solvent compositions were all amorphous, with single glass transition temperatures, different morphology and wettability. Compared with the pure drug, the dissolution rates of ITRA solid dispersions were improved significantly. Spray-dried powders stored at accelerated stability condition (90℃) showed significant differences in the physical stability.CONCLUSION Cosolvent for spray drying has a remarkable influence on the physical properties of ITRA solid dispersion. The difference in the physical properties was attributed to the different ITRA solubility in cosolvent leading to a different drug precipitation time in spray drying droplets, which further influence the drug distribution behavior and physical stability of solid dispersion.