Novel Solid Lipid Nanocarrier of Glibenclamide: A Factorial Design Approach with Response Surface Methodology

Background: In the present investigation, a factorial design approach attempt was applied to develop the Solid Lipid Nanoparticles (SLN) of Glibenclamide (GLB) a poorly water-soluble drug (BCS -II) used in the treatment of type 2 diabetes. Objectives: Prime objectives of this experiment are to optimize the SLN formulation of Glibenclamide and improve the therapeutic effectiveness of the developed formulation. Methods: Glibenclamide loaded SLNs (GLB-SLN) were fabricated by High speed homogenization technique. A 3(2)-factorial design approach has been employed to assess the influence of two independent variables, namely amount of Poloxamer 188 and Glyceryl Monostearate on entrapment efficiency (% EE) (Y1), Particle Size (nm) (Y2), % drug release at 8hr Q8 (Y3) and 24 hr Q24 (Y4) of prepared SLNs. Differential scanning calorimetry analysis revealed the compatibility of the drug into lipid matrix with a surfactant, while Transmission electron and Scanning electron microscopy studies indicated the size and shape of SLN. Results: The entrapment efficiency, particle size, Q8 and Q24 of the optimized SLNs were 88.93%, 125 nm, 31.12 +/- 0.951% and 86.07 +/- 1.291% respectively. Optimized GLB-SLN formula was derived from an overlay plot. Three-dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. In vivo testing of the GLB-SLN in diabetic albino rats demonstrated the significant antidiabetic effect of GLB-SLN. Conclusion: The hypoglycemic effect obtained by GLB-SLN remained significantly higher than that given by drug alone and marketed formulation, further confirming the higher therapeutic effectiveness of the GLB-SLN formulation. Our findings suggested the feasibility of the investigated system for oral administration of Glibenclamide.