Electrospun fibers of polyurethane [PU] and [PU/HPC] with or without drug loaded were successfully fabricated by electrospinning technique. The structures of the PU/ hydroxypropyl cellulose (HPC) electrospun fiber loaded with Donepezil (DP) were characterized using Fourier Transform Infrared Spectroscopy (FTIR). UV-Visible spectrophotometer and Electrochemical Impedance Spectroscopy (EIS) are used to determine drug release from the electrospun fiber in buffer solution. The electrochemical impedance spectroscopy data were fitted with Electrical Circuit Model of (R(Q(RW))(QR)) which gives a good correlation between the calculated and the experimental values. Electrochemical measurements gave more accurate results according to UV-Visible results for drug release which can be alternative and easy way to determine the drug release from the electrospun fiber. EIS measurements indicated that Warburg Impedance (W) was decreased and charge transfer resistance (Rct(2)) was increased according to the increasing of the amount of HPC in the formulation. The morphology of the electrospun fibers indicated that diameters of the electrospun fibers depends on the presence of HPC content and drug molecule.