Haloperidol Loaded Solid Lipid Nanoparticles for Nose to Brain Delivery: Stability and In vivo Studies

Abstract

In the present study, Haloperidol loaded solid lipid nanoparticles were prepared to enhance its uptake to brain via intranasal route. SLNs were prepared by modified emulsification diffusion technique. For optimization, a three factors and three levels Box - Behnken design was applied to study the effect of independent variables (factors) i.e. drug to lipid ratio (A), surfactant concentration (B) and stirring speed (C) on dependent variables (responses) i.e. particles size (Y1), entrapment efficiency (Y2), and drug loading (Y3). The value of optimized variables for HP-SLNs was 1:2 (drug to lipid ratio), 1.625% (surfactant concentration) and 3000 rpm (stirring speed). The optimized HP-SLNs formulation was evaluated for stability and in vivo studies. Stability studies revealed no significant (P<0.5) change was observed in particle size, zeta potential, entrapment efficiency and drug loading of optimized HP-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. A significant drop (P<0.001) in zeta potential was also observed at 40 ± 2°C/75 ± 5% RH after 3 months. In vivo studies were performed on albino Wistar rats and various pharmacokinetic and brain targeting parameters were determined. The pharmacokinetic parameters in brain after i.n. administration of HP-SLNs were found to be, Tmax 2 h, Cmax 329.17 ± 20.89 ng/mL, AUC0 - ∞ 2389.17 ± 78.82 ng.h/mL, Ke 0.079 ± 0.0065 h-1 and MRT 12.60 ± 0.99 h. The value of brain targeting parameters like drug targeting index, drug targeting efficiency and nose to brain direct transport were found to be 23.62, 2362.43% and 95.77% and 11.28, 1128.61% and 91.14% for HP-SLNs i.n. and HP Sol i.n. respectively.