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.
Lehto
P
P
Department of Pharmacology and Clinical Pharmacology, University of Turkey, Finland.
Laine
K
K
Kivistö
K T
KT
Neuvonen
P J
PJ
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