EFFECT OF DISSOLUTION RATE AND FOOD ON ORAL BIOAVAILABILITY OF BROPIRIMINE TABLETS IN DOGS

Three different tablet formulations of bropirimine were evaluated in a n in vitro dissolution study. Further, the effect of dissolution rate of bropirimine and food on the bioavailability after oral administrati on of the tablets was investigated in dogs. A tablet formulation with lower bropirimine content percent and smaller tablet size showed faste r in vitro dissolution rate due to the larger tablet surface area per unit mass of bropirimine and the higher ratio of hydrophilic excipient s in a tablet. In the fasted state, the bioavailability of bropirimine after oral administration of tablets tended to reflect the in vitro d issolution characteristics. The bioavailability after administration o f tablets with slow in vitro dissolution rate was increased by food in take 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, th ere were no differences in the plasma concentration profile and pharma cokinetic parameters of bropirimine between the tablets with a slow an d a fast in vitro dissolution rate. This suggests that the postprandia l administration of bropirimine tablets may maximize the bioavailabili ty without distinction of the in vitro dissolution rate.