Enhancing bioavailability and controlling the release of glibenclamide from optimized solid lipid nanoparticles

The objective of this study was to explore the possibility of incorporation of a poorly water soluble drug glibenclamide (GLB) into solid lipid nanoparticles (SLNs), which offer advantages of extended drug release and improved oral bioavailability. SLNs were prepared via emulsification followed by ultrasonication technique. Solubility studies were performed to identify appropriate lipid for preparation of SLNs. The effect of inclusion of different types of lipids and surfactants was investigated. Pharmacolcinetic, pharmacodynamic and histological finding of optimized SLNs were performed on rats. Stability of GLB-SLNs at 25(circle)C and 4(circle)C was investigated. Results revealed that changing type or concentration of lipid or surfactant had a pronounced effect on entrapment efficiencies (E.E), particle size, and release behavior of the SLNs. Physicochemical characterization showed GLB was in amorphous state, nanometer range and pharmacophore was preserved. GLB-SLNs showed extended drug release than dissolution of GLB suspension. Oral administration of optimized SLNs to diabetic rats led to significant reduction in blood glucose level with short onset time (0.5 h) and long duration of effect (24 h). Stability study recommended 4(circle)C as optimum storage temperature of SLNs. In this study, we confirmed that SLNs of GLB had beneficial effects on controlling diabetes in diabetic rats. (C) 2017 Elsevier B.V. All rights reserved.