Three versatile formulations (F1, F2, and F3) of orodispersible films (ODFs) containing donepezil hydrochloride were prepared from cellulose derivatives by solvent casting technique for the treatment of Alzheimer’s disease. The interaction between polymer and drug was investigated by spectral methods including UV, FTIR and 1H NMR and by microscopy techniques including AFM, SEM, and optical examination. Fourier transform infrared spectroscopy (FTIR) confirmed the compatibility of drug and polymer in ODF formulations. Hydrogen bonding interaction was studied by 1H NMR spectroscopy. Atomic force microscopy (AFM) of F3 films showed an average roughness of 75.34 nm and irregular particle size. According to scanning electron microscopy (SEM) data, the average particle size in F1, F2, and F3 films was 30, 37 and 50 μm, respectively. ODFs containing CMC-sodium in combination with HPMC (F3) showed faster disintegration of drug (93.01%) in comparison to F1, F2, and marketed formulation. ODF films of F3 formulation showed high surface roughness and greater pore size, which favored better and faster drug release properties. © 2017, Springer Science+Business Media, LLC, part of Springer Nature.