Developing a Modular Continuous Drug Product Manufacturing System with Real Time Quality Assurance for Producing Pharmaceutical Mini-Tablets.
Developing a Modular Continuous Drug Product Manufacturing System with Real Time Quality Assurance for Producing Pharmaceutical Mini-Tablets.
复制标题
开发具有实时质量保证的模块化连续药品制造系统，用于生产药物迷你片剂。
DOI：
10.1016/j.xphs.2023.09.024
复制
发表时间：
2024
影响因子：
3.8
通讯作者：
Reklaitis,Gintaras
中科院分区：
文献类型：
--
作者：
Sundarkumar,Varun;Wang,Wanning;Mills,Madeline;Oh,SueWei;Nagy,Zoltan;Reklaitis,Gintaras
制药业对开发用于生产医药产品的小规模模块化制造系统表现出浓厚的兴趣。这些系统提供敏捷和灵活的制造，非常适合用于需要快速生产药物的情况，如流行病和人道主义灾难。创建这样的系统需要开发用于制造固体口服药物产品的模块化设施。然而，近年来，这类设施的发展进展有限。本研究提出了一个原型模块化系统，使用按需滴（DoD）打印生产个性化的固体口服药物产品的发展。该系统的操作被证明用于生产迷你片剂，一类儿科药品，在连续和半批量模式。在这个过程中，DoD打印机用于生成熔融的配方液滴，这些液滴被固化成迷你片剂。然后在与打印机集成的连续过滤和干燥单元中提取、洗涤和干燥这些剂量。系统中还包含过程监控工具，用于真实的实时跟踪产品的关键质量属性和生产操作的关键过程参数。还提出了未来的创新领域，以改进该原型单元，并使基于该平台的先进药物制造系统的开发成为可能。
The pharmaceutical industry has shown keen interest in developing small-scale modular manufacturing systems for producing medicinal products. These systems offer agile and flexible manufacturing, and are well-suited for use in situations requiring rapid production of drugs such as pandemics and humanitarian disasters. The creation of such systems requires the development of modular facilities for making solid oral drug products. In recent years, however, the development of such facilities has seen limited progress. This study presents a development of a prototype modular system that uses drop on demand (DoD) printing to produce personalized solid oral drug products. The system's operation is demonstrated for manufacturing mini-tablets, a category of pediatric drug products, in continuous and semi-batch modes. In this process, the DoD printer is used to generate molten formulation drops that are solidified into mini-tablets. These dosages are then extracted, washed and dried in a continuous filtration and drying unit which is integrated with the printer. Process monitoring tools are also incorporated in the system to track the critical quality attributes of the product and the critical process parameters of the manufacturing operation in real time. Future areas of innovation are also proposed to improve this prototype unit and to enable the development of advanced drug manufacturing systems based on this platform.