THE EFFECT OF PH ON THE IN-VITRO DISSOLUTION OF 3 2ND-GENERATION SULFONYLUREA PREPARATIONS - MECHANISM OF ANTACID-SULFONYLUREA INTERACTION

Simultaneously administered magnesium hydroxide or sodium bicarbonate can increase the rate and extent of absorption of non-micronized glibe nclamide and glipizide. To clarify the mechanism of this interaction w e have studied the effect of pH on the dissolution of two different fo rmulations of glibenclamide (micronized and non-micronized) and one fo rmulation of glipizide. One tablet of each sulphonylurea preparation w as placed in a dissolution chamber containing continuously mixed disso lution medium at pH 2, pH 6 or pH 9; 5 mL of the medium was replaced e very 2 min. The amount of glibenclamide dissolved from the non-microni zed formulation within 2 h, was 1.2, 4.5 and 76% at pH 2, pH 6 and pH 9, respectively (P < 0.01), whereas 21, 29 and 100% was dissolved from the micronized formulation (P < 0.01). The amount of glipizide dissol ved within 2 h at pH 2, pH 6 and pH 9 was 3.9, 24 and 92%, respectivel y (P < 0.01). We conclude that the elevated pH of the gastric contents is the most likely explanation for the interactions previously demons trated between antacids and sulphonylureas after their concomitant ing estion.