Advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals
This dissertation describes advanced crystallization and precipitation strategies to improve process efficiency and product quality of biopharmaceuticals using bioactive glycopeptide vancomycin hydrochloride (Van) and protein lysozyme (LYZ) as the model biopharmaceuticals. The first study focuses on...
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| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
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Nanyang Technological University
2023
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| Online Access: | https://hdl.handle.net/10356/164549 |
| _version_ | 1811680113850318848 |
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| author | Pu, Siyu |
| author2 | Kunn Hadinoto Ong |
| author_facet | Kunn Hadinoto Ong Pu, Siyu |
| author_sort | Pu, Siyu |
| collection | NTU |
| description | This dissertation describes advanced crystallization and precipitation strategies to improve process efficiency and product quality of biopharmaceuticals using bioactive glycopeptide vancomycin hydrochloride (Van) and protein lysozyme (LYZ) as the model biopharmaceuticals. The first study focuses on the phase behavior of salting-out room-temperature crystallization of Van to determine crystallization conditions (i.e., pH, salt and peptide’s concentrations, incubation time) to avoid needle-shaped crystal formation. The second study compared the antisolvent (with organic solvent) and salting-out methods in their precipitation efficiency and product qualities of Van. In the third study, we evaluated for the first time the use of continuous slug flow crystallizer (CSFC) in bulk seeded protein crystallization, using lysozyme (LYZ) as the model protein. Lastly, in the fourth study, we developed a segmented slug flow crystallizer (SFC) of LYZ operated at a short residence time to improve the width of the crystal size distribution (CSD) and CSD’s reproducibility. |
| first_indexed | 2024-10-01T03:19:54Z |
| format | Thesis-Doctor of Philosophy |
| id | ntu-10356/164549 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:19:54Z |
| publishDate | 2023 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1645492023-03-06T07:30:04Z Advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals Pu, Siyu Kunn Hadinoto Ong School of Chemical and Biomedical Engineering KunnOng@ntu.edu.sg Engineering::Chemical engineering This dissertation describes advanced crystallization and precipitation strategies to improve process efficiency and product quality of biopharmaceuticals using bioactive glycopeptide vancomycin hydrochloride (Van) and protein lysozyme (LYZ) as the model biopharmaceuticals. The first study focuses on the phase behavior of salting-out room-temperature crystallization of Van to determine crystallization conditions (i.e., pH, salt and peptide’s concentrations, incubation time) to avoid needle-shaped crystal formation. The second study compared the antisolvent (with organic solvent) and salting-out methods in their precipitation efficiency and product qualities of Van. In the third study, we evaluated for the first time the use of continuous slug flow crystallizer (CSFC) in bulk seeded protein crystallization, using lysozyme (LYZ) as the model protein. Lastly, in the fourth study, we developed a segmented slug flow crystallizer (SFC) of LYZ operated at a short residence time to improve the width of the crystal size distribution (CSD) and CSD’s reproducibility. Doctor of Philosophy 2023-02-01T08:43:30Z 2023-02-01T08:43:30Z 2022 Thesis-Doctor of Philosophy Pu, S. (2022). Advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/164549 https://hdl.handle.net/10356/164549 10.32657/10356/164549 en 10.1016/j.ces.2022.118057 10.1016/j.cherd.2021.05.011 10.1016/j.cherd.2020.05.004 10.1016/j.ces.2020.116181 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |
| spellingShingle | Engineering::Chemical engineering Pu, Siyu Advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals |
| title | Advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals |
| title_full | Advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals |
| title_fullStr | Advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals |
| title_full_unstemmed | Advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals |
| title_short | Advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals |
| title_sort | advanced strategies to enhance the performances of crystallization and precipitation of biopharmaceuticals |
| topic | Engineering::Chemical engineering |
| url | https://hdl.handle.net/10356/164549 |
| work_keys_str_mv | AT pusiyu advancedstrategiestoenhancetheperformancesofcrystallizationandprecipitationofbiopharmaceuticals |