THE ROLE OF TROMETHAMINE AS A DISSOLUTION AND BIOAVAILABILITY ENHANCER OF ORAL GLIBENCLAMIDE

The dissolution rate, pharmacokinetic and pharmacodynamic of 3.5 mg gl ibenclamide formulations without and with increasing amounts of tromet hamine or PEG 6000 have been investigated The rate and extent of disso lution were increased in simulated intestinal fluids (pH 7) with incre asing tromethamine content. In the contrary, the amounts of dissolved drug in simulated gastric fluids (pH 1.02) were scar-eely detectable f or all samples and showed no significant difference. Similar results w ere obtained with increasing amount of polyethylene glycol except for those in acidic pH where a slight increase in drug dissolution was obt ained. In terms of plasma glibenclamide concentration or plasma glucos e concentration-time profiles, the bioavailability studies in rabbits showed no significant difference among all samples containing increasi ng amount of tromethamine. However, increasing the amount of polyethyl ene glycol produced a proportional increase in the amount of glibencla mide absorbed and a consequent decrease in plasma glucose concentratio n. Enteric coated formulations containing tromethamine increased drug absorption in vivo as indicated by the increased glibenclamide concent ration and a consequent plasma glucose reduction.