Present investigation evaluated permeability enhancing potential of pharmaceutical excipients (HPMC, PVP, Tween-80, Cremophor EL, Cremophor RH40, Transcutol, Labrasol and pluronics F-68) on the intestinal permeability of a P-glycoprotein substrate (domperidone). Everted and non-everted rat gut sacs were used for permeability studies. The investigation revealed that serosal to mucosal (S-M) transport of domperidone was greater than the mucosal to serosal (M-S) transport, which indicates that net movement of domperidone was towards lumen. Further, it was observed that S-M flux of domperidone was reduced by surfactant such as Tween-80, Cremophor EL, Cremophor RH40, Transcutol, Labrasol and pluronics F-68. Pluronics F-68 showed inhibitory effect at higher concentration (0.8 % w/v), but no significant inhibition was observed at lower concentrations. Polymers like HPMC and PVP did not produce any remarkable effect on the permeability of domperidone. The findings suggested that some of the excipients may be used to increase the permeability and absorption of P-gp substrates. However, their role should be confirmed at molecular level and clinical relevance of these findings should be evaluated.
