Effect of Dissolution Rate and Food on Oral Bioavailability of Bropirimine Tablets in Dogs

Abstract

Three different tablet formulations of bropirimine were evaluated in an in vitro dissolution study. Further, the effect of dissolution rate of bropirimine and food on the bioavailability after oral administration of the tablets was investigated in dogs. A tablet formulation with lower bropirimine content percent and smaller tablet size showed faster in vitro dissolution rate due to the larger tablet surface area per unit mass of bropirimine and the higher ratio of hydrophilic excipients in a tablet. In the fasted state, the bioavailability of bropirimine after oral administration of tablets tended to reflect the in vitro dissolution characteristics. The bioavailability after administration of tablets with slow in vitro dissolution rate was increased by food intake due to the in vivo dissolution increased in the fed state, while the postprandial effect on the bioavailability of tablets with fast in vitro dissolution rate was not clearly observed. In the fed state, there were no differences in the plasma concentration profile and pharmacokinetic parameters of bropirimine between the tablets with a slow and a fast in vitro dissolution rate. This suggests that the postprandial administration of bropirimine tablets may maximize the bioavailability without distinction of the in vitro dissolution rate.