Abstract
Effect of cyclodextrins on the permeability of P-glycoprotein substrate was assesed using everted gut sac technique and single pass in situ perfusion experiment. The in situ experiment was performed by using rabbit as animal model. Transport of domperidone was measured across duodenum and jejunum of rabbits in presence and absence of cyclodextrins. The in vitro observations showed that mucosal to serosal transport of domperidone was improved in presence of cyclodextrins. The order of cyclodextrins efficacy on M-S permeability of domperidone was beta-CyD > alpha-CyD >= gamma-CyD. The S-M/M-S permeability ratio of domperidone was also decreased by alpha-CyD (fold-5), beta-CyD (fold-2.5) and gamma-CyD (fold-5). In situ apparent jejunal permeability (PeA/L) of domperidone was also increased in presence of alpha-, beta-, and gamma-CyDs. The apparent duodenal permeability was slightly increased by gamma-CyD, but alpha-CyD and beta-CyD did not showed any significant effect. Results obtained from in vitro and in situ experiments indicate that cyclodextrins enhances the permeation and absorption of P-glycoprotein substrate domperidone.