Journal
COMPUTERS & CHEMICAL ENGINEERING
Volume 107, Issue -, Pages 77-91Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.compchemeng.2017.02.030
Keywords
Flowsheet modeling; Sensitivity analysis; Design space; Continuous pharmaceutical manufacturing; Optimization
Funding
- FDA [DHHS - FDA - 1 U01 FD005295-01]
- National Science Foundation Engineering Research Center on Structured Organic Particulate Systems [NSF-ECC 0540855]
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Continuous manufacturing has attracted increasing research attention in the pharmaceutical industry within the last decade. Based on the extensive experimental studies, numerous modeling and computational approaches have been developed to capture the process information and make predictions. Moreover, flowsheet models have been built to simulate the dynamic behaviors of a plant-wide manufacturing process with respect to different process input factors. However, there still lacks a systematic way to make the best use of flowsheet models in pharmaceutical processes. In this work, we propose a framework of process analysis and optimization for the continuous pharmaceutical manufacturing process where flowsheet models are available. Specifically, sensitivity analysis is conducted to identify the input factors that are most influential on the output; feasibility analysis is then implemented to characterize the design space in the high-dimensional space. Finally, process optimization is performed to find the optimal operation conditions that result in the minimum cost. (C) 2017 Elsevier Ltd. All rights reserved.
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