Continuous Manufacturing of Controlled-Release Metoprolol Succinate Tablets by Novel Hot-Melt Fragmentation Technology

IF 5.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2026-04-03 DOI:10.1208/s12249-026-03389-4

Rajat Radhakrishna Rao, Naitik Jain, Vinay Rao, Indu Bhushan, Srinivas Mutalik

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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

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新型热熔破碎法制备琥珀酸美托洛尔控释片

采用热熔造粒-双螺杆连续法制备琥珀酸美托洛尔片中片体系，可实现24小时的精准缓释。考虑了聚合物组成、捏合温度、螺杆转速和进料速度等关键配方和工艺参数，采用质量设计法对片中片体系进行了优化，以确保重现性和可扩展性。三层结构被定制为按时间顺序释放药物，允许外部，中间和核心隔间有助于逐渐和可预测的释放曲线，接近零级动力学。理化性质证实了琥珀酸美托洛尔在聚合物基体中的稳定性。此外，在大鼠体内的研究支持缓释行为，而加速稳定性测试表明，保留配方的完整性和溶出性能为三个月。这项工作描述了一种可扩展和强大的口服控释剂型平台的开发和评估，该平台可以作为传统单层或基于颗粒的系统的实际替代方案。图形抽象

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.