Continuous Manufacturing of Controlled-Release Metoprolol Succinate Tablets by Novel Hot-Melt Fragmentation Technology
Year: 2026
Type: article
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.
Source: AAPS PharmSciTech
Authors: Rajat Radhakrishna Rao, Naitik Jain, Vinay Rao, Indu Bhushan, Srinivas Mutalik
Institution: Manipal Academy of Higher Education
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,190
OpenAlex ID: W7148403110