Various types of tartaric acid, metoprolol free base and metoprolol tartrate containing Eudragit RS-based films were prepared and physicochemically characterized. In particular, the water uptake and compound release kinetics were monitored upon exposure to 0.1 M HCl, phosphate buffer pH 7.4 and distilled water. Appropriate analytical solutions of Fick's second law of diffusion, considering the given initial and boundary conditions, were used to elucidate the underlying mass transport mechanisms. Furthermore, the apparent diffusion coefficients of water, tartaric acid, metoprolol free base and metoprolol tartrate in the different Eudragit RS-based networks were determined. Importantly, the diffusivity of metoprolol tartrate and metoprolol free base significantly increased with increasing initial drug content, illustrating the strong plasticizing capacity of these compounds for the polymer. In contrast to Eudragit RL-based films, metoprolol free base precipitation occurred only at higher initial drug loadings, due to the lower water uptake resulting from the lower contents of quaternary ammonium groups. Interestingly, negatively charged tartrate ions diffused out more rapidly from metoprolol tartrate containing films than positively charged metoprolol ions, indicating that the lower molecular weight over-compensates the attractive ionic interactions with the positively charged macromolecules.