Formulation, Optimization, and Ex vivo Permeation Study of Ritonavir-loaded Solid Lipid Nanoparticles.

内容摘要

Ritonavir (RTV) is an antiviral drug that prevents human immunodeficiency virus (HIV). However, it has low bioavailability, which can be improved with the assistance of Solid Lipid Nanoparticles (SLNs). The present work aimed to formulate and optimize RTV-loaded SLNs using Box-Behnken design and evaluate the permeability coefficient using ex vivo permeation studies. RTV-SLNs were prepared using the ultrasonication technique. The SLN formulation was optimized based on particle size, % entrapment efficiency, and % cumulative drug release using response surface methodology resulting from Box-Behnken design. The Fourier-Transform Infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and transmission Electron Microscopy (TEM) studies were carried out for the characterization of optimized SLN formulation. Ex vivo permeation studies were also performed using chicken ileum. The optimized RTV-SLNs had a particle size of 270.34 nm, polydispersity index of 0.157, and zeta potential of -25.2 mV. The % entrapment efficiency and % cumulative drug release were found to be 94.33% and 67.13%, respectively. The FT-IR study revealed that SLNs showed no significant interactions between the drug and lipid in the formulation. The % crystalline index of the RTV-loaded SLN formulation was found to be 44.31% compared to the reference value of 100% for lipids. TEM analysis showed spherical nanoparticles that were uniform in shape. The release kinetics data demonstrated the drug release behavior, followed by the Korsmeyer-Peppas model, and suggested that the release from SLNs followed the non-fiction diffusion. The permeability coefficient of optimized SLN formulation was found to be significantly (p < 0.05) more compared to free RTV suspension. The enhancement ratio results suggested that RTV-SLNs permeated significantly (p < 0.05) faster (approximately 3.5 times) as compared to free RTV suspension. The optimized RTV-SLNs could be a promising carrier for improving the oral bioavailability of RTV.