The Effect of pH on the In-vitro Dissolution of Three Second-generation Sulphonylurea Preparations: Mechanism of Antacid-sulphonylurea Interaction

Abstract

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.

Role of Adenosine Triphosphate-Sensitive Potassium Channel Inhibition in Shock States

“…Another unresolved issue is that common sulfonylureas are practically insoluble in aqueous solution (58). Because no i.v.…”

In-vitro In-vivo Correlation Models for Glibenclamide after Administration of Metformin/Glibenclamide Tablets to Healthy Human Volunteers

“…This erratic absorption pattern results in glibenclamide plasma pro®les having delayed peaks, as reported previously (Ikegami et al 1985;Negebauer et al 1985). The double peak phenomenon observed for glibenclamide plasma pro®les in this study can be due to two reasons, either poor absorption in certain regions of the gastrointestinal tract or poor dissolution of glibenclamide, whose solubility is low and dependent on pH and particle size (Lehto et al 1996). An earlier study (Brockmeier et al 1985) showed that glibenclamide is absorbed from all sites in the gastrointestinal tract.…”

Parenteral administration of glipizide sodium salt, an inhibitor of adenosine triphosphate-sensitive potassium channels, prolongs short-term survival after severe controlled hemorrhage in rats*

“…Glipizide (glydiazinamide) possesses a pyrazine moiety, which is basic. This property suggests that water solubility of glipizide may be improved by converting it into a pharmacologically acceptable salt, for example, a sodium salt (15). Glipizide sodium salt was prepared in situ at 300 mg/mL with stoichiometric sodium bicarbonate in 10% glycerol/deionized water (v/v).…”

“…Since all of the sulfonylureas are practically insoluble in aqueous solution (15), additional formulation studies are required to identify a salt of a clinically approved K ATP channel inhibitor suitable for parenteral administration. Moreover, intramuscular administration of drugs involves additional requirements, including a low volume of injection and appropriate absorption and distribution.…”