Formulation and In Vitro Evaluation of Glibenclamide Solid Dispersion Tablets with Enhanced Dissolution Rate

Abstract

Glibenclamide is practically insoluble in water and its GI absorption is limited by its dissolution rate. This study was conducted to improve the solubility and dissolution properties of glibenclamide using solid dispersion technique. The carriers used were polyethylene glycol (PEG) 6000 and polyvinyl pyrrolidone (PVP) K-30 with or without sodium lauryl sulphate (SLS) in different weight ratios and prepared by solvent evaporation, melting and physical mixing techniques. PVP K-30 was used only for solvent evaporation method. Equilibrium solubility, in vitro dissolution, fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies were performed. Equilibrium solubility and in vitro dissolution studies showed remarkable improvements in drug solubility and release from the solid dispersions and physical mixtures as compared to the drug alone. This can be attributed to the improved wettability, dispersibility and decreased crystallinity of the drug, particularly in the solid dispersions. The ternary solid dispersion of the drug with PVP K-30 at a ratio of 1:5 with SLS showed the highest dissolution rate of 94.41 ± 0.47% in comparison to pure drug (30.26 ± 0.06%), binary solid dispersion (86.71 ± 0.57%), physical mixture (57.72 ± 0.88%) and other solid dispersions. Solid dispersion prepared with PVP K-30 showed better improvement in solubility and dissolution rate of glibenclamide than PEG 6000. Glibenclamide with PEG 6000 solid dispersions by melting method showed highest dissolution relative to the solvent evaporation. The dissolution rate of glibenclamide was directly proportional to increment in proportion of the carrier. The results obtained from FTIR spectroscopy showed good evidence of drugcarrier compatibility for those solid dispersions that showed highest dissolution and solubility. Crystallinity of the drug was reduced in the solid dispersions as revealed by the DSC thermograms. The results suggested that solid dispersion with selected excipients is a powerful tool to accelerate the dissolution of glibenclamide, a poorly water-soluble drug.

Keywords: glibenclamide, solid dispersion, PEG 6000, PVP K-30, dissolution