Experimental study of ketoconazole impregnation into polyvinyl pyrrolidone and hydroxyl propyl methyl cellulose using supercritical carbon dioxide: Process optimization

This study aims to increase the oral bioavailability of ketoconazole (KET, drug) by incorporating it into water-soluble polymers, using supercritical carbon dioxide (SC-CO2) as the impregnating solvent. For this purpose, loading of KET into poly (vinylpyrrolidone) (PVP) and hydroxy propyl methyl cellulose (HPMC) using supercritical solvent impregnation (SSI) was investigated for the first time. Box-Behnken design (BBD) was used to optimize the impregnation process. Effects of three process parameters, namely pressure (150, 200 and 250 bar), impregnation time (60, 120 and 180 min), and temperature (308, 318 and 328 K) on the loading were studied, leading to a range of 0.33% 0.98% for KET into PVP and 0.46% 1.41% for KET into HPMC polymer. Samples were examined using FTIR, DLS, SEM, XRD and DSC analyses. Additionally, the small particle size and the presence of polymers increased the dissolution rate of the drug in aqueous solutions up to 7.3 folds.

Automated summary

This study aims to enhance the oral bioavailability of ketoconazole by incorporating it into water-soluble polymers using supercritical carbon dioxide as the impregnating solvent. The loading of ketoconazole into poly (vinylpyrrolidone) and hydroxy propyl methyl cellulose using supercritical solvent impregnation was investigated for the first time. The optimization of the impregnation process was conducted using Box-Behnken design, and the effects of pressure, impregnation time, and temperature on the loading were studied. The results showed that the small particle size and the presence of polymers significantly increased the dissolution rate of the drug in aqueous solutions.