Salting-Out crystallization of glycopeptide Vancomycin: phase behavior study to control the crystal habit
Needle-shaped crystals pose downstream processing issues in pharmaceutical manufacturing. Strategies to avoid needle-shaped crystal formation have been developed for small-molecule and protein pharmaceuticals. Controlling crystal habit of peptides, whose molecular weight lies between small molecules...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2022
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/163454 |
| _version_ | 1811688390657048576 |
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| author | Pu, Siyu Hadinoto, Kunn |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Pu, Siyu Hadinoto, Kunn |
| author_sort | Pu, Siyu |
| collection | NTU |
| description | Needle-shaped crystals pose downstream processing issues in pharmaceutical manufacturing. Strategies to avoid needle-shaped crystal formation have been developed for small-molecule and protein pharmaceuticals. Controlling crystal habit of peptides, whose molecular weight lies between small molecules and proteins, has never been investigated. The present work studied phase behavior of salting-out room-temperature crystallization of glycopeptide vancomycin to determine crystallization conditions to avoid needle-shaped crystal formation. Batch crystallizations of prominent crystal habits identified from phase behavior study (i.e., needle and non-needle) were subsequently performed. Batch crystallization's products were evaluated in their production yield/capacity, purity, size distribution, thermal stability, interfacial water content, dissolution profile, and antibiotic activity. The results showed octahedral crystals as the predominant habit produced at higher yield across the range of pH, salt/peptide concentrations investigated. Needle crystal formation was avoided by pH and salt concentration controls. Both crystal habits exhibited many similar properties, but with distinct thermal stability and dissolution profiles. |
| first_indexed | 2024-10-01T05:31:27Z |
| format | Journal Article |
| id | ntu-10356/163454 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:31:27Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1634542022-12-07T01:11:11Z Salting-Out crystallization of glycopeptide Vancomycin: phase behavior study to control the crystal habit Pu, Siyu Hadinoto, Kunn School of Chemical and Biomedical Engineering Engineering::Chemical engineering Protein Crystallization Crystal Shape Needle-shaped crystals pose downstream processing issues in pharmaceutical manufacturing. Strategies to avoid needle-shaped crystal formation have been developed for small-molecule and protein pharmaceuticals. Controlling crystal habit of peptides, whose molecular weight lies between small molecules and proteins, has never been investigated. The present work studied phase behavior of salting-out room-temperature crystallization of glycopeptide vancomycin to determine crystallization conditions to avoid needle-shaped crystal formation. Batch crystallizations of prominent crystal habits identified from phase behavior study (i.e., needle and non-needle) were subsequently performed. Batch crystallization's products were evaluated in their production yield/capacity, purity, size distribution, thermal stability, interfacial water content, dissolution profile, and antibiotic activity. The results showed octahedral crystals as the predominant habit produced at higher yield across the range of pH, salt/peptide concentrations investigated. Needle crystal formation was avoided by pH and salt concentration controls. Both crystal habits exhibited many similar properties, but with distinct thermal stability and dissolution profiles. Ministry of Education (MOE) The authors would like to acknowledge the research funding from Ministry of Education Singapore (Grant No. AcRF Tier 1 RG82/20). 2022-12-07T01:11:11Z 2022-12-07T01:11:11Z 2022 Journal Article Pu, S. & Hadinoto, K. (2022). Salting-Out crystallization of glycopeptide Vancomycin: phase behavior study to control the crystal habit. Chemical Engineering Science, 262, 118057-. https://dx.doi.org/10.1016/j.ces.2022.118057 0009-2509 https://hdl.handle.net/10356/163454 10.1016/j.ces.2022.118057 2-s2.0-85137302579 262 118057 en RG82/20 Chemical Engineering Science © 2022 Elsevier Ltd. All rights reserved. |
| spellingShingle | Engineering::Chemical engineering Protein Crystallization Crystal Shape Pu, Siyu Hadinoto, Kunn Salting-Out crystallization of glycopeptide Vancomycin: phase behavior study to control the crystal habit |
| title | Salting-Out crystallization of glycopeptide Vancomycin: phase behavior study to control the crystal habit |
| title_full | Salting-Out crystallization of glycopeptide Vancomycin: phase behavior study to control the crystal habit |
| title_fullStr | Salting-Out crystallization of glycopeptide Vancomycin: phase behavior study to control the crystal habit |
| title_full_unstemmed | Salting-Out crystallization of glycopeptide Vancomycin: phase behavior study to control the crystal habit |
| title_short | Salting-Out crystallization of glycopeptide Vancomycin: phase behavior study to control the crystal habit |
| title_sort | salting out crystallization of glycopeptide vancomycin phase behavior study to control the crystal habit |
| topic | Engineering::Chemical engineering Protein Crystallization Crystal Shape |
| url | https://hdl.handle.net/10356/163454 |
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