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 and enhance 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 created from 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 by SLNs which showed improvement in the oral bioavailability of the drug.

Lipid Nanoparticles for Drug Delivery

“…Then the melted lipids are mixed with an aqueous surfactant solution to produce nanoemulsions using high-pressure homogenization (HPH), microemulsions, high-speed stirring or ultrasonication, and membrane emulsification. [52][53][54][55] Dispersed SLNs can be obtained by cooling the nanoemulsions in an ice bath. [28] Several factors have been reported to influence NP formation and their properties, including homogenization time, sonication time, surfactant concentration, lipid concentration, drug concentration, lipid type, and surfactant type.…”

Lipid-Based Nanoparticles for Drug/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development

“…In the homogenization process, melted lipids are mixed with drugs and a preheated aqueous phase containing surfactants. The mixture undergoes high-pressure homogenization for several cycles to achieve the desired nanoparticle size. , Alternatively, ultrasonication involves homogenizing the aqueous phase with surfactants and melted lipids using high-speed stirring, followed by ultrasonication to break down large particles into smaller droplets …”

“…The mixture undergoes high-pressure homogenization for several cycles to achieve the desired nanoparticle size. 153,154 Alternatively, ultrasonication involves homogenizing the aqueous phase with surfactants and melted lipids using high-speed stirring, followed by ultrasonication to break down large particles into smaller droplets. 155 However, the nonsolvent emulsification technique involves complex procedures and multistep processes, leading to a potential batch-to-batch variation.…”