Characteristics of intestinal absorption of adinazolam and in vivo evaluation of oral sustained release tablets of adinazolam in beagle dogs

Abstract

The characteristics of intestinal absorption of adinazolam in rats were investigated using an in situ intestinal loop method on the upper, middle and lower parts of the small intestine, and colon. The disappearance of the drug from the intestinal lumen was measured to estimate the absorption. Adinazolam was readily absorbed from various sites of the small intestine and colon indicating no absorption site specificity. Absorption followed first-order kinetics with a disappearance half-life of less than 15 min. Dose dependency or saturation of the absorption were not observed in the experimental concentration range of 5–1000 μg/ml. In one of the experiments to investigate the effect of postprandial administration, the intestinal absorption of adinazolam decreased somewhat when the administered solution contained either 5% bile powder or 5% polysorbate 80. In the biopharmaceutic study, the sustained release (SR) tablet significantly prolonged the plasma adinazolam concentration in beagle dogs in comparison to that of the rapidly disintegrating conventional tablets (conventional tablet) of adinazolam. The mean residence time (MRT) of adinazolam from the SR tablets was about 5-times greater than that of the conventional tablets.