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Digital design and optimization of an integrated reaction-extraction-crystallization-filtration continuous pharmaceutical process
conference contribution
posted on 2022-03-10, 10:18 authored by Tim CampbellTim Campbell, Chris RiellyChris Rielly, Brahim BenyahiaBrahim BenyahiaThis work investigates the digital design of a continuous pharmaceutical plant comprising a continuous three stage reaction, liquid-liquid extraction, multistage cooling and antisolvent crystallization, and wash-filtration. Firstly, the mathematical models were developed and validated in conjunction with the available experimental data obtained from the literature and research partners. The resulting digital twin was used for steady state optimization to deliver optimal options for plant design and operation, including process capacities and number of crystallization stages. After the identification of the optimal design and optimal steady state operation, the digital twin was used to perform uncertainty propagation and global sensitivity analysis to identify the Critical Process Parameters (CPP) and Critical Material Attributes (CMA) and deliver robust and cost-effective methods for a systematic implementation of Quality-by-Design (QbD). This approach is aimed at demonstrating that the plant can be operated within the robust quality bounds which provide a built-in quality assurance for the final product. Several Critical Quality Attributes (CQA) which impact drug safety and efficacy were considered which includes the average crystal size, crystal size distribution, coefficient of variation and product purity were considered as the CQA.
History
School
- Aeronautical, Automotive, Chemical and Materials Engineering
Department
- Chemical Engineering
Published in
32nd European Symposium on Computer Aided Process Engineering: ESCAPE-32Pages
775-780Source
32nd European Symposium on Computer Aided Process Engineering (ESCAPE32)Publisher
ElsevierVersion
- AM (Accepted Manuscript)
Rights holder
© ElsevierPublisher statement
This paper was accepted for publication in the 32nd European Symposium on Computer Aided Process Engineering: ESCAPE-32 and the definitive published version is available at https://doi.org/10.1016/B978-0-323-95879-0.50130-2.Acceptance date
2022-01-24Publication date
2022-08-01Copyright date
2022ISBN
9780323958790; 9780323958806ISSN
1570-7946Publisher version
Book series
Computer Aided Chemical Engineering; Volume 51Language
- en