Enhancement of dissolution amount and in vivo bioavailability of itraconazole by complexation with beta-cyclodextrin...

The main objective of this study was to improve the inclusion formation between itraconazole and beta-cyclodextrin and thus enhance dissolution amount and bioavailability characteristics of itraconazole. Inclusion complexes between itraconazole and beta-cyclodextrin were prepared using simple physical mixing, conventional coprecipitation method, and supercritical carbon dioxide (SC CO(2)). Effects of process variables (temperature, pressure) and drug:cyclodextrin ratio on inclusion yield and thermal behavior of the solid complexes prepared by SC CO(2) were studied and compared to those obtained by physical mixing and coprecipitation methods. In addition, dissolution amounts of the products obtained by different methods were measured in gastric fluid. Finally, pharmacokinetic studies of the inclusion complexes were conducted in male Wistar rats to assess the bioavailability of the prepared complexes. Results showed that temperature, pressure and itraconazole:beta-cyclodextrin ratio had significant effects on the inclusion yield of the complex prepared by SC CO(2) method. Higher inclusion yields were obtained in the SC CO(2) method as compared to physical mixing and coprecipitation methods. In vivo drug pharmacokinetic studies showed that the itraconazole-beta-cyclodextrin product prepared using SC CO(2) gave higher bioavailability of itraconazole (in blood, liver and kidney of male Wistar rats) as compared to the products obtained by physical mixing or coprecipitation methods.