Augmented Oral Bioavailability and Prokinetic Activity of Levosulpiride Delivered in Nanostructured Lipid Carriers

Abstract

The present study is aimed to develop and optimize levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for improving oral bioavailability and prokinetic activity of LSP. LSP-NLCs were optimized with D-optimal mixture design using solid lipid, liquid lipid and surfactant concentrations as independent variables. The prepared LSP-NLCs were evaluated for physicochemical properties and solid-state characterization. The in vivo oral pharmacokinetics and prokinetic activity of LSP-NLCs were evaluated in rats. LSP-NLCs formulation was optimized at Precirol® ATO 5/Labrasol (80.55/19.45%, w/w) and Tween 80/Span 80 concentration of 5% (w/w) as a surfactant mixture. LSP-NLCs showed a spherical shape with a particle size of 152 nm, a polydispersity index of 0.230 and an entrapment efficiency of 88%. The DSC and PXRD analysis revealed conversion of crystalline LSP to amorphous state after loading into the lipid matrix. LSP-NLCs displayed a 3.42- and 4.38-flods increase in AUC and Cmax after oral administration compared to LSP dispersion. In addition, LSP-NLCs showed enhanced gastric emptying (61.4%), intestinal transit (63.0%), and fecal count (68.8) compared to LSP dispersion (39.7%, 38.0% and 51.0, respectively). Taken together, these results show improved oral bioavailability and prokinetic activity of LSP-NLCs and presents a promising strategy to improve therapeutic activity of LSP for efficient treatment of gastric diseases.

Keywords

• levosulpiride
• nanostructured lipid carriers
• D-optimal mixture design
• oral bioavailability
• prokinetic activity
• gastric disorders