Abstract: OBJECTIVE To prepare donepezil hydrochloride extended-release tablets by hydrophilic gel-forming matrix materials and assess the quality. METHODS Combined with two types of hydrophilic gel-forming matrix material HPMC K100LV and HPMC K4M. Donepezil hydrochloride extended-release tablets were manufactured by the dry granulation process. The formulations were optimized by orthogonal experiment design utilizing dissolution similarity f2 as an evaluation index. The drug content and impurity were analyzed by the HPLC method. The stability study was conducted under an accelerated and long-term conditions. RESULTS The optimized formulation of donepezil hydrochloride extended-release tablets showed acceptable quality and stability and similar dissolution profiles with the brand product. CONCLUSION The prepared donepezil hydrochloride extended-release tablets are feasible.