Formulation and pharmacokinetic evaluation of rifampicin solid lipid nanoparticles

Abstract

This study aims to optimize RIF loaded solid lipid nanoparticles (RIF-SLNs) to sustain its release andenhance its oral absorption and bioavailability. RIF loaded SLNs were formulated by a modified micro emulsionbased technique using two different lipids (Cetyl palmitate and Glyceryl monostearate) and two different surfactants(Tween®80 and Poloxamer 188). Particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (E.E), drug loading capacity (L.C), in vitro drug release, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) were determined for RIF loaded SLNs formulae. Pharmacokinetic study was performed on optimized RIF-SLNs, marketed RIF and pure drug suspension in Wistar rats. The particle size, PDI, E.E% and L.C% of optimized formula were recorded as 0.183 µm, 0.420, -34.7 mV, 80.8% and 0.216%, respectively. In vitro release studies suggested that all SLNs formulae possessed a burst release createdfrom the unloaded drug and adsorbed drug molecules at SLNs surface then sustained release due to diffusion of drug from lipid matrix over a period of 120 h. From the release kinetics data, the release rate of RIF from all formulae fitted into Higuchi’s diffusion model. Pharmacokinetic study showed significant enhancement in RIF-SLNs relative bioavailability 5.86 and 2.33 folds in comparison with pure RIF suspension and marketed RIF. RIF loaded SLNs were formulated successfully by a modified micro emulsion-based method. Also, oral drug delivery can be enhanced bySLNs which showed improvement in the oral bioavailability of the drug.