Gliclazide microcrystals prepared by two methods of in situ micronization: pharmacokinetic studies in diabetic and normal rats.

The low water-solubility of gliclazide (GL) leads to a low dissolution rate and variable bioavailability. The aim of this study was to investigate the effect of micronization on the absorption and pharmacokinetics of GL after oral administration in rats. GL microcrystals were prepared using solvent-change and pH-shift methods. Scanning electron microscopy showed considerable changes in the shape and size of crystals using both methods. In the optimized formulation of each method, the particle size of treated GL was reduced about 30 (from 290 to 9.9 microm) and 61 times (to 4.76 microm) by solvent-change and pH-shift methods, respectively. Recrystallized samples showed faster dissolution rate than untreated GL particles. Glucose-lowering effect, C(max), and area under the drug concentration-time profile (area under the curve (AUC)) were compared in diabetic and normal rats. AUC and C(max) were increased by microcrystals in both groups of animals. Administration of 40 mg/kg of GL in the form of untreated drug and microcrystals obtained by solvent-change and pH-shift methods caused 12.49% and 21.04% enhancement in glucose-lowering effect of GL in diabetic rats, respectively.