The coatings in osmotic tablets play a critical role in controlling the release of active pharmaceutical ingredient. Coatings are formed by spraying dilute polymer solution onto the tablet surface. During drying, the films develop shrinkage stress, which can cause cracking. The coatings are also subject to large tensile stress generated by osmotic pressure during the dissolution process, which may rupture the coating. Despite the role of tensile stress in causing fracture in osmotic tablet coatings, a rigorous quantification of the drying stress, mechanical properties and microstructure is missing. The present work fills this gap via detailed measurement of drying stress, Young’s modulus and fracture properties of osmotic tablet coatings of cellulose acetate mixed with two different plasticisers, namely polyethylene glycol and hydroxypropyl cellulose. The measurements were complemented with imaging of the surface and the cross-section of films using scanning electron microscopy so as to relate the drying stress and mechanical properties to the microstructure of the films. The phase separation during the drying process increases the pore size, while simultaneously decreasing the modulus and the peak drying stress of the drying films. The results suggest that films with strong adhesion to the tablet surface will not rupture but if the films delaminate, the drying stress are sufficiently large to cause rupture. The detailed study presented here provides guidelines to the formulator for designing rupture-free osmotic coatings.