Formulation, Characterization and Pharmacokinetic Evaluation of Amorphous Solid Dispersions of Glibenclamide for Bioavailability Enhancement in Wistar Rats

Abstract

Oral bioavailability of Glibenclamide (Glb) was appreciably improved by forming amorphous solid dispersion (ASD) with Poloxamer-188 (P-188). Poloxamer-188 substantially enhanced the solubility and thereby dissolution rate of the BCS Class-II drug, Glibenclamide (Glb) and simultaneously exhibited better stabilizing effect of amorphous solid dispersion prepared by solvent evaporation method. The physical state of the dispersed Glibenclamide in the polymeric matrix was characterized by differential scanning calorimetry, X-ray diffraction, scanning electron microscope and Fourier Transform Infrared studies. In vitro drug release in buffer (pH 7.2) revealed that amorphous solid dispersion at the Glb-P-188 ratio of 1:6 (SDE4) improved the dissolution of Glibenclamide 90% within 3 hrs. Pharmacokinetic study of the solid dispersion formulation (SDE4) formulation in wistar rats showed that oral bioavailability of the drug was greatly increased as compared to market tablet formulation, Daonil(R). Solid dispersion formulation (SDE4) resulted in approximately two fold higher AUC0-24 hrs. Solid dispersion formulation (SDE4) formulation was found stable during the study period of six months.