Gliclazide-loaded Solid Lipid Nanoparticles: preparation & Intestinal permeability investigation

Abstract

Introduction and Background: Gliclazide, a sulfonylurea specifically used for the treatment of non-insulin-dependent diabetes mellitus. This drug exhibits slow GI absorption rate and wide inter-individual variations in absorption and bioavailability. Moreover, because of its poor water solubility, it is impossible to prepare aqueous solutions of this compound for oral or other routs of administration.Therefore, we hypothesize that these limitations could be waived by entrapping gliclazide inside a lipid carrier like Solid Lipid Nanoparticles. In the present investigation, we prepared and characterized SLNs of Gliclazide with suitable size and drug entrapment efficiency. The intestinal absorption characteristics of prepared nanoparticles assessed to estimate the in vivo bioavailability of the preparations. Aim: Preparation and in vitro and in vivo evaluation of solid lipid nanoparticles for controlled oral delivery of Gliclazide.Methods: Single-Pass Intestinal Perfusion was performed in isolated jejunal segment at SLN formulation of Gliclazide to compare intestinal permeability changes against of simple solution of gliclazide. Phenol red was used as a non-absorbable marker. Stability studies were conducted to ensure that the loss of gliclazide could be attributed to intestinal absorption. Outlet samples were analysed using the developed HPLC method and effective permeability values were calculated by respected formula.Results: The effective permeability value of Gliclazide simple solution in the jejunum was 0.00805 cm/min. Also the effective permeability values of SLN.Gliclazide nanoparticles found to be 0.0167 cm/min. The use of Solid Lipid Nanoparticles led to a significant increase in intestinal permeability of gliclazide. Discussion and conclusion: In conclusion, the high aqueous solubility of Gliclazide might be a crucial factor for its poor oral bioavailability. New techniques have shown that the use of nanoparticles like SLN can dramatically increase intestinal permeability.