Protein binding of glipizide using equilibrium dialysis technique: effects of hydrogen ion concentration, drug concentration and ionic strength.

The objective of this research was to investigate the effects of hydrogen ion concentration, drug concentration and ionic strength on the binding affinity of glipizide to albumin protein. Different buffer solutions of different pH values (pH 6.7, 7.5 and 8.5), different drug concentrations (2.45 mg, 4.82 mg and 9.42 mg), and phosphate buffer solutions pH 7.5 of different ionic strength (0.1, 0.4 and 1.0) were prepared. The effects of pH, drug concentration and ionic strength on the amount of glipizide bounded to 0.25 g bovine albumin was investigated. As the pH of the solution was increased from pH 6.4 to pH 8.5, milligrams drug bounded to gram protein (r value) decreased from 8.2 mg to 3.84 mg/g protein. Also as the ionic strength of the solution was increased from 0.1 to 1.0, the r value decreased from 10.76 mg to 3.96 mg/g protein. However, the r value did not change significantly with increasing of drug from 2.45 mg to 9.42 mg/25 ml. The r value was 7.36 mg/g protein when concentration of the drug was 2.45 mg/25 ml and 7.4 mg/g protein when the concentration of the drug was 9.42 mg/25 ml. This study demonstrated that factors such as high pH and high ionic strength can alter drug-protein binding and consequently increase free drug in plasma and increase bioavailability of slightly water insoluble drug such as antidiabetic drugs.