Zein, an alcohol-soluble protein contained in the endosperm tissue of Zea mais, occurs as a by-product of corn processing. Although zein has been empirically employed as an edible coating for foods and pharmaceuticals for decades, it has not attracted considerable attention as a possible alternative for film-forming agents in drug formulations such as derivatives of cellulose or polyacrylates. In this report, the thermal, thermomechanical, water sorption and gas barrier properties of zein and plasticized mixtures of zein are discussed. With the objective of classifying these properties within the field of polymers used as pharmaceutical film formers, zein was compared with various types of ethyl cellulose that had a degree of substitution (DS) in the range 1.7–2.6. In order to quantify the plasticizing efficiency of low molecular weight compounds when added to zein, the compatibility of the mixtures was investigated by means of dynamic-mechanical thermal analysis (DMTA). The esters of tartaric acid were found to have superior properties with respect to miscibility, depression of the glass transition temperature and reduced water sorption of the respective mixtures. With regard to solvent-free extrusion, pressure-volume-temperature measurements were performed on mixtures of zein and diethyl tartrate and evaluated according to the Simha-Somcynsky equation of state for multicomponent systems. Generally, the results give reason to believe that zein might serve as an inexpensive and most effective substitute for the fast-disintegrating synthetic and semi-synthetic film coatings currently used for the formulation of substrates that allow extrusion coating.