Robust in vitro drug release behavior is an important feature of extended release (ER) hydrophilic matrix formulations for accurate prediction of in vivo drug release. In this study, ER hydrophilic matrix tablets of metoprolol tartrate were formulated using a high viscosity grade of hypromellose as a rate-limiting polymer. Expectedly, this formulation showed an undesirable initial burst release followed by controlled drug release. Application of a barrier membrane (BM) coating of ethylcellulose with a pore former (hypromellose) resulted in the elimination of the burst effect. The aim of this study was to investigate the robustness of in vitro metoprolol release from BM-coated hydrophilic matrix tablets by simulating the physicochemical properties of gastrointestinal fluids and mechanical stress in the fasted- and fed state human gastrointestinal (GI) tract. Uncoated and BM-coated matrices were subjected to various dissolution studies simulating the varying pH conditions and additional physicochemical parameters, and the mechanical stress that can be caused by GI motility during both fasted and fed state GI passage. The BM-coated formulation showed robust drug release without an initial burst in all test scenarios. BM-coated matrix formulations thus represent a very promising approach for obtaining a highly controlled and robust drug release from oral ER formulations.