In vitro and in vivo evaluation of donepezil-sustained release microparticles for the treatment of Alzheimer's disease.

The purpose of this work is to prepare donepezil microparticles (DM) and evaluate its advantage as a sustained release delivery system with subcutaneous injection once a month. DM was prepared using poly (d,l-lactide-co-glycolide) (PLGA) by an oil-water emulsion solvent evaporation technique. DM showed the loading ratio 13.2+/-2.1% (w/w) and yield 54.8+/-0.8% with mean particle size about 75mum. In vitro release of DM showed that donepezil completely released within 28 days in water, but the cumulative release percentages up to day 30 were 98.4% and 49.1% for phosphate buffer saline (PBS, pH 5.8) and PBS (pH 7.4), respectively. The in vivo experiment demonstrated that DM (90mg/kg) produced a sustained release process in rats, and reached steady-state concentration at day 8 and maintained until day 27 with steady-state levels of donepezil between 130.3+/-7.8 and 121+/-9.8ng/ml, which was accordance with that of free donepezil by oral application route (3mg/kgday). DM (90mg/kg) by subcutaneous infusion in rats produced the same pharmacological role as free donepezil (3mg/kgday) by oral application route. These results implicated that DM as a sustained release delivery strategy could substitute for its oral formulation for therapy of AD and come true its administration once a month.