Abstract A novel metoprolol succinate tablet-in-tablet-in-tablet system was developed using hot-melt granulation combined with twin-screw continuous processing to provide an accurate 24-h sustained release. Tablet-in-tablet-in-tablet system was optimized using Quality by Design, considering key formulation and process parameters such as polymer composition, kneading temperature, screw speed, and feed rate to ensure reproducibility and scalability. The three-layer architecture was tailored to release the drug in a timed sequence, allowing the outer, middle, and core compartments to contribute to a gradual and predictable release profile that closely approached zero-order kinetics. Physicochemical characterization confirmed the stability of metoprolol succinate within the polymeric matrix. Additionally, in vivo studies in rats supported the sustained release behaviour, while accelerated stability testing indicated retention of formulation integrity and dissolution performance for three months. This work describes the development and evaluation of a scalable and robust platform for controlled-release oral dosage forms which could serve as a practical alternative to conventional single-layer or pellet-based systems. Graphical Abstract
Rao et al. (Fri,) studied this question.