The highly variable physiological conditions within the gastrointestinal tract can cause variable drug release and absorption from the orally administrated dosage forms. The emptying of the gastric content is one of the most critical physiological processes, dictating the amount of the active ingredient available for absorption into the systemic circulation. In this study, we prepared two water gastric emptying regimes on advanced gastric simulator (AGS) with programmable “pyloric” valve. Gastric emptying regimes were designed in such a way to capture the main findings of the MRI (magnetic resonance imaging) in vivo studies, conducted under fasted conditions according to the EMA and FDA guidelines for bioavailability and bioequivalence studies. Four immediate release formulations containing a model drug of BCS class III were tested. Comparative dissolution tests were also performed with the USP2 apparatus. In vitro release profiles were compared to the in vivo data in order to evaluate the importance of gastric emptying for subsequent absorption of the active substance from the tested formulations. Our bio-relevant in vitro dissolution model showed good discriminatory power for all of the tested formulations. Moreover, a better relation to in vivo data was achieved with AGS with respect to the tested conventional dissolution method.