OPTIMIZATION, CHARACTERIZATION AND IN VIVO STUDY OF RIVASTIGMINE TARTRATE NANOPARTICLES BY USING 22 FULL FACTORIAL DESIGN FOR ORAL DELIVERY

Abstract

Objective: This research aims to optimize the solid lipid nanoparticles by using full factorial design to improve the delivery of rivastigmine tartrate (RT), which is used for the treatment of Alzheimer’s disease (AD). Solid lipid nanoparticles (SLNs) are attracting importance for drug developers due to their performance. The outcome of this research will lead to improvements in drug release and solubility of RT for better therapeutic effect. Methods: Four different methods were used to prepare solid lipid nanoparticles of rivastigmine tartrate, namely the modified solvent emulsification technique, the microemulsion cooling technique, the solvent injection technique, and the homogenization/ultrasonication technique. Glyceryl monostearate (GMS) was used as a lipid; Compritol 888, tween 80, and span 40 were used as surfactants, co-surfactants, and stabilizers, respectively. Results: SLNs were evaluated for zeta potential, particle size, polydispersity index, surface morphology, Fourier Transform Infrared Spectroscopy (FTIR), and differential scanning calorimetry (DSC). Entrapment efficiency and drug loading were also estimated. Solubility study of rivastigmine tartrate in different solid lipids as well as the in vitro drug release, was studied. The particle size of SLNs was found to range between 138.22+0.01 nm and 172.79+0.23 nm. The zeta potential of the optimized formulation was found to be in the the-24+0.01mV range, indicating a stable formulation. A scanning electron microscope indicates a clear spherical structure without any aggregation. Entrapment efficiency was determined to be 69.27+0.22%. The RT-SLNs showed significant retention in memory when compared with RT solution (standard formulation), which may be attributed to the lipid nature and nanostructure of the delivery system that may probably result in more accumulation of the drug in the brain to show better effect. Conclusion: The current study concludes that the microemulsion cooling technique is the best method for patient compliance and stability with all desired characteristics parameters.