Enhancement of dissolution of glyburide by solid dispersion and lyophilization techniques

Abstract

Glyburide (GLY) is an oral hypoglycemic agent that is poorly soluble in water. The present study describes the preparation of solid dispersions and lyophilization of the dispersions designed to increase the solubility. Solid dispersions of GLY were prepared using polyethylene glycol 4000 (PEG 4000), PEG 6000 and a mixture of PEG 4000 and PEG 6000 (h1 mixture). The effect of melt and solvent methods of preparation of solid dispersion on dissolution behavior was also investigated. Dissolution studies indicated a significant increase in dissolution of GLY when dispersed in PEGs. Physical mixtures containing PEGs also showed improved dissolution of GLY as compared with that of pure drug, indicating the solubilizing effect of PEGs. Solid dispersions containing GLY/PEG 6000, 1:8, showed a 14-fold increase in dissolution after 60 min (D60) and another dispersion containing GLY/PEG 4000, 1:10, showed an 8-fold increase in the phosphate buffer system. The dispersion containing six parts of the PEG mixture (PEG 4000/PEG 6000, 1:1 mixture) showed a 12-fold increase in D60 as compared with pure drug. When multi-carrier solid dispersion containing six parts of mixture was prepared by the solvent method, the D60 value was about 2-fold that of the same dispersion prepared by the melt method. The dissolution of lyophilized solid dispersions further increased the dissolution of GLY significantly.