Abstract
The aim of the present research is to characterize the leakage of intestinal constituents induced by β-cyclodextrin (β-CyD) derivatives using an in situ perfusion and an in vitro everted sac. The efficacy of 6-O-α-D-glucosyl (G1)- and 6-O-α-D-maltosyl (G2)-β-CyDs as oral carriers was also compared with that of 2-hydroxypropyl-(HP1; average molar degree of substitution, 0.9) and 2, 6-di-O-methyl (DM)-β-CyDs. In the in situ studies, phenol red (PR) penetration and the release profiles of intestinal constituents for G2-β-CyD were fairly close to those for HP1-β-CyD. However, the ability of G2-β-CyD to include cholesterol was greater than that of HP1-β-CyD. To characterize the release of intestinal constituents induced by modified β-CyDs, the capability of including cholesterol was held constant between DM- and branched β-CyDs. The everted sac study showed that the amount of DM-β-CyD transferred to the serosal side was not significantly different from the branched β-CyDs. On the serosal side, the amount of cholesterols released was approximately 3 times higher for DM-β-CyD than for the branched β-CyDs at 60 min. The cumulative amounts of cholesterols for DM-β-CyD increased approximately 6 times at 60 min compared with at 30 min, predominating over the leakage (average 2.6-fold) on the mucosal side. In contrast, the exposure of the branched β-CyDs resulted in an insignificant increase over the period of this experiment.The present study suggests that permeable β-CyD derivatives play an important role in the leakage of intestinal components. G2-β-CyD is preferably recommended as a drug solubilizer in oral formulations as well as HP1-β-CyD, based on the lower release of intestinal constituents.
