Cuboidal lipid polymer nanoparticles of rosuvastatin for oral delivery

Abstract

The present work aimed to develop and characterize sustained release cuboidal lipid polymeric nanoparticles (LPN) of rosuvastatin calcium (ROS) by solvent emulsification-evaporation process. A three factor, two level (2³) full-factorial design was applied to study the effect of independent variables, i.e. amount of lipid, surfactant and polymer on dependent variables, i.e. percent entrapment efficiency and particle size. Optimized formulations were further studied for zeta potential, TEM, in vitro drug release and ex vivo intestinal permeability. Cuboidal nanoparticles exhibited average particle size 61.37 ± 3.95 nm, entrapment efficiency 86.77 ± 1.27% and zeta potential −6.72 ± 3.25 mV. Nanoparticles were lyophilized to improve physical stability and obtain free-flowing powder. Effect of type and concentration of cryoprotectant required to lyophilize nanoparticles was optimized using freeze-thaw cycles. Mannitol as cryoprotectant in concentration of 5-8% w/v was found to be optimal providing zeta potential −20.4 ± 4.63 mV. Lyophilized nanoparticles were characterized using FTIR, DSC, XRD and SEM. Absence of C=C and C–F aromatic stretch at 1548 and 1197 cm⁻¹, respectively, in LPN indicated coating of drug by lipid and polymer. In vitro diffusion of ROS using dialysis bag showed pH-independent sustained release of ROS from LPN in comparison to drug suspension. Intestinal permeability by non-everted gut sac model showed prolonged release of ROS from LPN owing to adhesion of polymer to mucus layer. In vivo absorption of ROS from LPN resulted in 3.95-fold increase in AUC_0–last and 7.87-fold increase in mean residence time compared to drug suspension. Furthermore modified tyloxapol-induced rat model demonstrated the potential of ROS-loaded LPN in reducing elevated lipid profile.

Keywords:

• Precirol^® ATO 5
• Kollidon^® 30
• 23 factorial design
• solvent evaporation emulsification
• lipid polymeric nanoparticles
• cuboidal shaped
• modified tyloxapol-induced hyperlipidemia
• pharmacokinetic study

Acknowledgements

The authors would like to thank Astra Lifecare (India) Pvt. Ltd., Gattefosse India Pvt. Ltd. and BASF India Pvt. Ltd. for providing gift samples. Authors are grateful to Dr. Agnivesh Shrivastava for providing expertise in experimental design that greatly assisted the research. Authors extend their thanks to SVKM’s NMIMS for providing infrastructure to carry out the work.

Disclosure statement

The authors report no declarations of interest.