Spray Dried Mucoadhesive Microparticles of Donepezil with Chitosan and Carbopol in Alzheimer’s Disease

Abstract

Background: The traditional oral formulation for Alzheimer’s disease treatment has the drawbacks of first-pass metabolism, plasma protein binding, and poor blood-brain barrier penetration. This study was conducted to establish the nasal route of administration for donepezil formulations in Alzheimer’s disease. Materials and Methods: Donepezil mucoadhesive microparticles synthesized by spray-drying and evaluated for Infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. The ex vivo study was done with Franz’s diffusion cell using goat nasal mucosa. The in vivo study was performed on the Albino rat’s nasal route for determining drug concentration by HPLC analysis in brain tissue at single-point evaluation. Results: The microparticles were with optimum size with no drug-polymer interaction in Infrared spectroscopy and Differential scanning calorimetry. Scanning electron microscopy exhibited morphology of spherical or ellipsoid microparticles with efficient drug entrapment. The percentage drug release for chitosan microparticles was 66.57 to 85.74 and for carbopol microparticles was 69.54 to 91.53 in the ex vivo permeability study. In vivo studies showed that drug concentrations of 110.48% to 114.92% for chitosan batches and 111.87% to 142.08% for carbopol batches were superior to controls. Conclusion: Ex vivo permeability study revealed drug release patterns with as high as 85.74% ±0.02 for DCH2 formulation and 91.53±0.3% for DC3 formulation. In in vivo study formulation DCH2 displayed drug concentration 110.87±6.87% and DC3 shown 129.51±9.82% over the control batch which is conclusive for improved drug delivery of donepezil through mucoadhesive microparticles for the nose to brain targeting in Alzheimer’s disease.