Donepezil Hydrochloride Loaded Solid Lipid Nanoparticles: Formulation, in Vitro–in Vivo Pharmacokinetic and Pharmacodynamics Evaluation

Abstract

Objective: The aim of the present study was to design and in vitro–in vivo evaluation of Donepezil Hydrochloride solid lipid nanoparticles (DHSLN). Methods: A modified solvent injection method was used to produce Donepezil-loaded solid lipid nanoparticles. A Response Surface Method 3-factor, 2-level Box-Behnken design was applied to study the effect of independent variables on dependent variables. Then it was coated with tween 80 for ease of permeability through the blood-brain barrier due to intact absorption of solid lipid nanoparticles. The prepared SLN was evaluated for particle size, zeta potential analysis, Entrapment efficiency, In vitro drug release study, Field Emission-scanning electron microscopy, In vivo Pharmacokinetic and Pharmacodynamics studies. Results: The results of coated optimized formulation showed an average particle size of 185.8 nm, entrapment efficiency of 78.52±2.54%, and in vitro drug release of 98.62±3.14% at 36h at pH 7.4. The pharmacokinetic data show higher Cmax and improved bioavailability, which was also supported by behavioural changes observed in locomotor activity for surface-modified SLN formulation. Conclusion: Thus, the current study successfully designed, developed an optimized SLN formulation. The surface-modified SLN proved to enhance the permeability of the drug through barrier, which led to the enhancement of Donepezil bioavailability and locomotor activity.

Formulation, Characterization and Optimization of Folic Acid-Tailored Daidzein Solid Lipid Nanoparticles for the Improved Cytotoxicity Against Colon Cancer Cells

“…Box-Behnken was selected because it was efficient and required fewer runs than the central composite design. ANOVA was used for statistical validation and to generate polynomial equations provided by design expert software [19][20][21].…”