Background: Switching from branded to generic extended-release (ER) metoprolol formulations is common practice due to cost considerations. Although generics are approved as bioequivalent, subtle differences in formulation, such as coating composition, may influence drug release under real-life conditions across patients. Objective: This study aimed to evaluate potential differences in drug release between the originator product Beloc-Zok 95 mg and randomly selected generic ER metoprolol succinate formulations available on the German market. Methods: Formulations were assessed under variable, interindividual, physiologically relevant in vitro conditions simulating gastrointestinal transit. Results: All formulations demonstrated controlled drug release; however, the release profiles were not fully overlapping. One generic formulation consistently exhibited slightly slower release across all test scenarios. These findings indicate that minor differences in release behavior can occur even among bioequivalent ER formulations. While such variations are generally clinically negligible, they may contribute to pharmacokinetic and pharmacodynamic differences in sensitive individuals, potentially explaining reported adverse effects such as bradycardia, hypotension, chest pain, or increased blood pressure when switching to generic products. Conclusions: The results underscore the importance of considering patient-specific variability when switching from branded to generic formulations. Incorporating physiologically relevant in vitro studies combined with physiologically based pharmacokinetic and pharmacodynamic modeling in future research may improve predictions of in vivo performance and support safer therapeutic decisions.
Karkossa et al. (Tue,) studied this question.