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Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling

[Image: see text] To facilitate integrated end-to-end pharmaceutical manufacturing using digital design, a model capable of transferring material property information between operations to predict product attributes in integrated purification processes has been developed. The focus of the work repor...

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Autores principales: Ottoboni, Sara, Brown, Cameron J., Mehta, Bhavik, Jimeno, Guillermo, Mitchell, Niall A., Sefcik, Jan, Price, Chris J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9764418/
https://www.ncbi.nlm.nih.gov/pubmed/36569418
http://dx.doi.org/10.1021/acs.oprd.2c00165
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author Ottoboni, Sara
Brown, Cameron J.
Mehta, Bhavik
Jimeno, Guillermo
Mitchell, Niall A.
Sefcik, Jan
Price, Chris J.
author_facet Ottoboni, Sara
Brown, Cameron J.
Mehta, Bhavik
Jimeno, Guillermo
Mitchell, Niall A.
Sefcik, Jan
Price, Chris J.
author_sort Ottoboni, Sara
collection PubMed
description [Image: see text] To facilitate integrated end-to-end pharmaceutical manufacturing using digital design, a model capable of transferring material property information between operations to predict product attributes in integrated purification processes has been developed. The focus of the work reported here combines filtration and washing operations used in active pharmaceutical ingredient (API) purification and isolation to predict isolation performance without the need of extensive experimental work. A fixed Carman–Kozeny filtration model is integrated with several washing mechanisms (displacement, dilution, and axial dispersion). Two limiting cases are considered: case 1 where there is no change in the solid phase during isolation (no particle dissolution and/or growth), and case 2 where the liquid and solid phases are equilibrated over the course of isolation. In reality, all actual manufacturing conditions would be bracketed by these two limiting cases, so consideration of these two scenarios provides rigorous theoretical bounds for assessing isolation performance. This modeling approach aims to facilitate the selection of most appropriate models suitable for different isolation scenarios, without the requirement to use overly complex models for straightforward isolation processes. Mefenamic acid and paracetamol were selected as representative model compounds to assess a range of isolation scenarios. In each case, the objective of the models was to identify the purity of the product reached with a fixed wash ratio and minimize the changes to the crystalline particle attributes that occur during the isolation process. This was undertaken with the aim of identifying suitable criteria for the selection of appropriate filtration and washing models corresponding to relevant processing conditions, and ultimately developing guidelines for the digital design of filtration and washing processes.
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spelling pubmed-97644182022-12-21 Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling Ottoboni, Sara Brown, Cameron J. Mehta, Bhavik Jimeno, Guillermo Mitchell, Niall A. Sefcik, Jan Price, Chris J. Org Process Res Dev [Image: see text] To facilitate integrated end-to-end pharmaceutical manufacturing using digital design, a model capable of transferring material property information between operations to predict product attributes in integrated purification processes has been developed. The focus of the work reported here combines filtration and washing operations used in active pharmaceutical ingredient (API) purification and isolation to predict isolation performance without the need of extensive experimental work. A fixed Carman–Kozeny filtration model is integrated with several washing mechanisms (displacement, dilution, and axial dispersion). Two limiting cases are considered: case 1 where there is no change in the solid phase during isolation (no particle dissolution and/or growth), and case 2 where the liquid and solid phases are equilibrated over the course of isolation. In reality, all actual manufacturing conditions would be bracketed by these two limiting cases, so consideration of these two scenarios provides rigorous theoretical bounds for assessing isolation performance. This modeling approach aims to facilitate the selection of most appropriate models suitable for different isolation scenarios, without the requirement to use overly complex models for straightforward isolation processes. Mefenamic acid and paracetamol were selected as representative model compounds to assess a range of isolation scenarios. In each case, the objective of the models was to identify the purity of the product reached with a fixed wash ratio and minimize the changes to the crystalline particle attributes that occur during the isolation process. This was undertaken with the aim of identifying suitable criteria for the selection of appropriate filtration and washing models corresponding to relevant processing conditions, and ultimately developing guidelines for the digital design of filtration and washing processes. American Chemical Society 2022-12-06 2022-12-16 /pmc/articles/PMC9764418/ /pubmed/36569418 http://dx.doi.org/10.1021/acs.oprd.2c00165 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Ottoboni, Sara
Brown, Cameron J.
Mehta, Bhavik
Jimeno, Guillermo
Mitchell, Niall A.
Sefcik, Jan
Price, Chris J.
Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling
title Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling
title_full Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling
title_fullStr Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling
title_full_unstemmed Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling
title_short Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling
title_sort digital design of filtration and washing of active pharmaceutical ingredients via mechanistic modeling
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9764418/
https://www.ncbi.nlm.nih.gov/pubmed/36569418
http://dx.doi.org/10.1021/acs.oprd.2c00165
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