Formulation and Evaluation of Glyceryl Behenate based Solid Lipid Nanoparticles for the Delivery of Donepezil to Brain through Nasal Route

Abstract

In the present study, Donepezil (DPL) loaded solid lipid nanoparticles (SLNs) were formulated for brain targeting through nasal route. SLNs were prepared by solvent emulsification diffusion technique using Glyceryl behenate as lipid and blend of tween 80 and poloxamer 188 (1:1) as surfactant. SLNs were evaluated for particle size, zeta potential, drug entrapment efficiency, In vitro drug release, stability and in vivo studies. For optimized formulation, in vitro drug release was found to be 96.72 ± 5.89% in 24 h and Higuchi model was found to be fitted with highest value of correlation coefficient (R2= 0.9504). Stability studies revealed no significant (P< 0.5) change in particle size, zeta potential, entrapment efficiency and drug loading of optimized DPL-SLNs formulation when it was stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months, but the size of particles was increased significantly (P?0.001) when the optimized formulation was stored at 40±2 °C /75±5% RH. In vivo studies were performed on albino wistar rats and various pharmacokinetic and brain targeting parameters were determined. The value of AUC 0-8 in brain for DPL-SLNs i.n. was found to be nearly 1.97 times higher than that of DPL-Sol. i.v., whereas 1.63 times superior than DPL-Sol. administered intranasally. The higher drug targeting efficiency (288.75%) and direct transport percentage (65.37%) with optimized formulation indicates better brain targeting efficiency as compared to other formulations.