Studies on drug absorption from oral cavity. II. Influence of the unstirred water layer on absorption from hamster cheek pouch in vitro and in vivo.

Abstract

The influence of the unstirred water layer (UWL) adjacent to the membrane surface of the hamster cheek pouch on absorption was studied in vitro and in vivo. The tissue uptake rate of 14C-laurylalcohol was determined in vitro and the value of the effective resistance of UWL (RW) was calculated. RW values were reduced by increasing the stirring rate of the mucosal solution. In vitro permeation of 14C-benzoic acid into the serosal compartment was also increased in the well-stirred condition. Thus, the existence of UWL as an effective diffusion barrier for drug absorption from the hamster cheek pouch was suggested. To clarify the influence of the existence of UWL on the absorption in vivo, the apparatus for luminal stirring was newly devised. When the luminal solution was well-stirred, the absorption of benzoic acid in the lower pH region significantly increased, resulting in the disappearance of the shift of pH-absorption curve for benzoic acid. Furthermore, the luminal stirring increased the absorption rate constant for salicylic acid. From these experimental results, it is suggested that UWL plays a part of barriers against drug permeation in the hamster cheek pouch.