The change in the water permeability, glass transition temperatures, and mechanical properties of ethyl cellulose with different degrees of substitution are presented. Studies of the hydroxyl group content on the polymer chains indicate that the mechanical properties of a free film decrease as the hydroxyl group content increases. This is thought to be due to the lower solubility of ethyl cellulose with a lower degree of substitution, as determined by the interaction constant in ethanol and the ability of the film with a high hydroxyl group content to hold more water. Furthermore, an increase in hydroxyl group content increases water permeability. Finally, a study of spray-coated pellets has been performed and reveals a similar effect. The higher the hydroxyl group content, the higher the release rate and, at the same time, the decrease in Vickers hardness.