Flexibility analysis for continuous ibuprofen manufacturing processes

doi:10.1016/j.cjche.2021.10.019

中国化学工程学报 ›› 2022, Vol. 51 ›› Issue (11): 115-125.DOI: 10.1016/j.cjche.2021.10.019

• Full Length Article • 上一篇下一篇

Flexibility analysis for continuous ibuprofen manufacturing processes

Wenhui Yang¹, Haoyu Yin², Zhihong Yuan¹, Bingzhen Chen³

1. State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;
2. School of Material Science and Engineering, Tsinghua University, Beijing 100084, China;
3. Department of Chemical Engineering, Tsinghua University, Beijing 100084, China

收稿日期:2021-08-11 修回日期:2021-10-13 出版日期:2022-11-18 发布日期:2023-01-18
通讯作者: Zhihong Yuan,E-mail:zhihongyuan@mail.tsinghua.edu.cn
基金资助:
The authors gratefully acknowledge the financial support from the National Key Research and Development Program of China (2018AAA0101602).

Flexibility analysis for continuous ibuprofen manufacturing processes

Wenhui Yang¹, Haoyu Yin², Zhihong Yuan¹, Bingzhen Chen³

1. State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;
2. School of Material Science and Engineering, Tsinghua University, Beijing 100084, China;
3. Department of Chemical Engineering, Tsinghua University, Beijing 100084, China

Received:2021-08-11 Revised:2021-10-13 Online:2022-11-18 Published:2023-01-18
Contact: Zhihong Yuan,E-mail:zhihongyuan@mail.tsinghua.edu.cn
Supported by:
The authors gratefully acknowledge the financial support from the National Key Research and Development Program of China (2018AAA0101602).

摘要/Abstract

摘要： Continuous ibuprofen (a widespread used analgesic drug) manufacturing is full of superiorities and is a fertile field both in industry and academia since it can not only effectively treat rheumatic and other chronic and painful diseases, but also shows great potential in dental diseases. As one of central elements of operability analysis, flexibility analysis is in charge of the quantitative assessment of the capability to guarantee the feasible operation in face of variations on uncertain parameters. In this paper, we focus on the flexibility index calculation for the continuous ibuprofen manufacturing process. We update existing state-of-the-art formulations, which traditionally lead to the max-max-max optimization problem, to approach the calculation of the flexibility index with a favorable manner. Advantages regarding the size of the mathematical model and the computational CPU time of the modified method are examined by four cases. In addition to identifying the flexibility index without any consideration of control variables, we also investigate the effects of different combinations of control variables on the flexibility property to reveal the benefits from taking recourse actions into account. Results from systematic investigations are expected to provide a solid basis for the further control system design and optimal operation of continuous ibuprofen manufacturing.

关键词: Continuous manufacturing, Pharmaceuticals, Mathematical modeling, Flexibility analysis, Mixed integer programing, Optimization

Abstract: Continuous ibuprofen (a widespread used analgesic drug) manufacturing is full of superiorities and is a fertile field both in industry and academia since it can not only effectively treat rheumatic and other chronic and painful diseases, but also shows great potential in dental diseases. As one of central elements of operability analysis, flexibility analysis is in charge of the quantitative assessment of the capability to guarantee the feasible operation in face of variations on uncertain parameters. In this paper, we focus on the flexibility index calculation for the continuous ibuprofen manufacturing process. We update existing state-of-the-art formulations, which traditionally lead to the max-max-max optimization problem, to approach the calculation of the flexibility index with a favorable manner. Advantages regarding the size of the mathematical model and the computational CPU time of the modified method are examined by four cases. In addition to identifying the flexibility index without any consideration of control variables, we also investigate the effects of different combinations of control variables on the flexibility property to reveal the benefits from taking recourse actions into account. Results from systematic investigations are expected to provide a solid basis for the further control system design and optimal operation of continuous ibuprofen manufacturing.

Key words: Continuous manufacturing, Pharmaceuticals, Mathematical modeling, Flexibility analysis, Mixed integer programing, Optimization

Wenhui Yang, Haoyu Yin, Zhihong Yuan, Bingzhen Chen. Flexibility analysis for continuous ibuprofen manufacturing processes[J]. 中国化学工程学报, 2022, 51(11): 115-125.

Wenhui Yang, Haoyu Yin, Zhihong Yuan, Bingzhen Chen. Flexibility analysis for continuous ibuprofen manufacturing processes[J]. Chinese Journal of Chemical Engineering, 2022, 51(11): 115-125.

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Flexibility analysis for continuous ibuprofen manufacturing processes

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