Drug-excipient interactions by Vitamin E-TPGS: in vitro studies on inhibition of P-glycoprotein and colonic drug absorption

Segments of rabbit colonic tissue were used to investigate the effect of the surface-active excipient Vitamin E-TPGS on colonic drug absorption. Transport studies in Ussing chambers revealed a statistically significant increase in apparent permeability (Papp) of the P-glycoprotein substrate colchicine in the presence of Vitamin E-TPGS from 1.8 to 2.6*10- 6 cm/s. The integrity of colonic tissue in these experiments was preserved as demonstrated by electron microscopy. The free fraction of colchicine was not affected by the presence of the surfactant, indicating that the surfactant had no solubilizing effect on the model drug used. However, Vitamin E-TPGS was confirmed to be a potent P-glycoprotein inhibitor (IC50 of approximately 0.8 μM) using P-glycoprotein competent endothelial cells. Results indicate that Vitamin E-TPGS has the potential to enhance drug permeability in colonic tissue, and for colchicine this effect was attributed to inhibition of P-glycoprotein.