Solid dispersions of mebendazole were prepared in view of improving its extent and rate of dissolution. The solid dispersions were prepared by hot melt extrusion method using water soluble polymers and isomalt, polyethylene glycol and triethyl citrate as plasticizer. Solubility studies showed that solubility of solid dispersions, pure drug and physical mixtures were higher in acidic dissolution medium. FT-IR studies showed that the drug was compatible with polymers and the characteristic peak of mebendazole disappeared in the extruded samples. DSC studies in combination with X-ray diffraction were carried out for the solid state characterization samples after melt extrusion. The extent and rate of mebendazole release was dependent on the composition of extrudates. The drug release stability was also dependent on the composition of melt extrudates which was supramolecularly tracked by positron annihilation lifetime spectroscopy based on the free volume changes of samples as a function of storage.