Uncertainty and Sensitivity Analysis for an Ibuprofen Synthesis Model Based on Hoechst Path

Research output: Chapter in Book/Report/Conference proceedingArticle in proceedingsResearchpeer-review

Abstract

The pharmaceutical industry faces several challenges and barriers when implementing new or improving current pharmaceutical processes, such as competition from generic drug manufacturers and stricter regulations from the U.S. Food and Drug Administration and the European Medicine agency. The demand for efficient and reliable models to simulate and design/improve pharmaceutical processes is therefore increasing. For the case of ibuprofen, a well-known anti-inflammatory drug, the existing models do not include its complete synthesis path, usually referring only to one out of aset of different reactions. To this end, we integrated different models in this work to obtain a comprehensive synthesis model for ibuprofen, in a MATLAB /Simulink modelinterface. The process flowsheet is based on the Hoechst path, starting from the Friedel-Craftsacetylation of isobutylbenzene to 4-isobutylphenylacetophenone, its further hydrogenation to IBPE (1-4isobutylphenylethanol) and the carbonylation to both ibuprofen and by-products. The integration of the referred models takes into account the different solvents used in reactions, as well as the presence of by-products and the irratios. In addition, the process path takes into consideration the effects of temperature, acidity, and the choice of the catalyst. Parameter estimation and uncertainty analysis were conducted on the kinetic model parameters using experimental data available in the literature. Finally, one factor at a time sensitivity analysis in the form of deviations in the main process inputs was made, allowing the study of the system behavior and time-response. This time-response is especially characteristic of the integrated model, asit consist of a combination of continuous and batch processes.The sensitivity analysis performed gives a good indication of the model behavior for further work, such as control implementation, plant-wide optimization, or upstream and downstream process integration.
Original languageEnglish
Title of host publicationProceedings of the 27th European Symposium on Computer Aided Process Engineering (ESCAPE 27)
EditorsAntonio Espuña, Moisès Graells, Luis Puigjaner
Volume40
PublisherElsevier
Publication date2017
Edition1
Pages153-168
ISBN (Print)9780444639653
ISBN (Electronic)9780444639707
DOIs
Publication statusPublished - 2017
Event27th European Symposium on Computer Aided Process Engineering - Barcelona, Spain
Duration: 1 Oct 20175 Oct 2017
Conference number: 27
https://www.elsevier.com/books/27th-european-symposium-on-computer-aided-process-engineering/espuna/978-0-444-63965-3

Conference

Conference27th European Symposium on Computer Aided Process Engineering
Number27
CountrySpain
CityBarcelona
Period01/10/201705/10/2017
Internet address

Keywords

  • Flowsheet modelling
  • Process design
  • ibuprofen synthesis
  • Sensitivity analysis

Cite this

da Conceicao Do Carmo Montes, F., Gernaey, K. V., & Sin, G. (2017). Uncertainty and Sensitivity Analysis for an Ibuprofen Synthesis Model Based on Hoechst Path. In A. Espuña, M. Graells, & L. Puigjaner (Eds.), Proceedings of the 27th European Symposium on Computer Aided Process Engineering (ESCAPE 27) (1 ed., Vol. 40, pp. 153-168). Elsevier. https://doi.org/10.1016/B978-0-444-63965-3.50029-5
da Conceicao Do Carmo Montes, Frederico ; Gernaey, Krist V. ; Sin, Gürkan. / Uncertainty and Sensitivity Analysis for an Ibuprofen Synthesis Model Based on Hoechst Path. Proceedings of the 27th European Symposium on Computer Aided Process Engineering (ESCAPE 27). editor / Antonio Espuña ; Moisès Graells ; Luis Puigjaner. Vol. 40 1. ed. Elsevier, 2017. pp. 153-168
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da Conceicao Do Carmo Montes, F, Gernaey, KV & Sin, G 2017, Uncertainty and Sensitivity Analysis for an Ibuprofen Synthesis Model Based on Hoechst Path. in A Espuña, M Graells & L Puigjaner (eds), Proceedings of the 27th European Symposium on Computer Aided Process Engineering (ESCAPE 27). 1 edn, vol. 40, Elsevier, pp. 153-168, 27th European Symposium on Computer Aided Process Engineering, Barcelona, Spain, 01/10/2017. https://doi.org/10.1016/B978-0-444-63965-3.50029-5

Uncertainty and Sensitivity Analysis for an Ibuprofen Synthesis Model Based on Hoechst Path. / da Conceicao Do Carmo Montes, Frederico; Gernaey, Krist V.; Sin, Gürkan.

Proceedings of the 27th European Symposium on Computer Aided Process Engineering (ESCAPE 27). ed. / Antonio Espuña; Moisès Graells; Luis Puigjaner. Vol. 40 1. ed. Elsevier, 2017. p. 153-168.

Research output: Chapter in Book/Report/Conference proceedingArticle in proceedingsResearchpeer-review

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AB - The pharmaceutical industry faces several challenges and barriers when implementing new or improving current pharmaceutical processes, such as competition from generic drug manufacturers and stricter regulations from the U.S. Food and Drug Administration and the European Medicine agency. The demand for efficient and reliable models to simulate and design/improve pharmaceutical processes is therefore increasing. For the case of ibuprofen, a well-known anti-inflammatory drug, the existing models do not include its complete synthesis path, usually referring only to one out of aset of different reactions. To this end, we integrated different models in this work to obtain a comprehensive synthesis model for ibuprofen, in a MATLAB /Simulink modelinterface. The process flowsheet is based on the Hoechst path, starting from the Friedel-Craftsacetylation of isobutylbenzene to 4-isobutylphenylacetophenone, its further hydrogenation to IBPE (1-4isobutylphenylethanol) and the carbonylation to both ibuprofen and by-products. The integration of the referred models takes into account the different solvents used in reactions, as well as the presence of by-products and the irratios. In addition, the process path takes into consideration the effects of temperature, acidity, and the choice of the catalyst. Parameter estimation and uncertainty analysis were conducted on the kinetic model parameters using experimental data available in the literature. Finally, one factor at a time sensitivity analysis in the form of deviations in the main process inputs was made, allowing the study of the system behavior and time-response. This time-response is especially characteristic of the integrated model, asit consist of a combination of continuous and batch processes.The sensitivity analysis performed gives a good indication of the model behavior for further work, such as control implementation, plant-wide optimization, or upstream and downstream process integration.

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da Conceicao Do Carmo Montes F, Gernaey KV, Sin G. Uncertainty and Sensitivity Analysis for an Ibuprofen Synthesis Model Based on Hoechst Path. In Espuña A, Graells M, Puigjaner L, editors, Proceedings of the 27th European Symposium on Computer Aided Process Engineering (ESCAPE 27). 1 ed. Vol. 40. Elsevier. 2017. p. 153-168 https://doi.org/10.1016/B978-0-444-63965-3.50029-5