The effect of pH on the in-vitro dissolution of three second-generation sulphonylurea preparations: mechanism of antacid-sulphonylurea interaction.
Simultaneously administered magnesium hydroxide or sodium bicarbonate can increase the rate and extent of absorption of non-micronized glibenclamide and glipizide. To clarify the mechanism of this interaction we have studied the effect of pH on the dissolution of two different formulations of glibenclamide (micronized and non-micronized) and one formulation of glipizide. One tablet of each sulphonylurea preparation was placed in a dissolution chamber containing continuously mixed dissolution medium at pH 2, pH 6 or pH 9; 5 mL of the medium was replaced every 2 min. The amount of glibenclamide dissolved from the non-micronized 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 dissolved within 2 h at pH 2, pH 6 and pH 9 was 3.9, 24 and 92%, respectively (P < 0.01). We conclude that the elevated pH of the gastric contents is the most likely explanation for the interactions previously demonstrated between antacids and sulphonylureas after their concomitant ingestion.
Department of Pharmacology and Clinical Pharmacology, University of Turkey, Finland.
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D000863:Antacids / Q000737:chemistry*; D005913:Glipizide / Q000737:chemistry*; D005905:Glyburide / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000737:chemistry*; D012995:Solubility; D013607:Tablets
D000863:Antacids; D007004:Hypoglycemic Agents; D013607:Tablets; D005905:Glyburide; D005913:Glipizide