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...

Full description

Saved in:
Bibliographic Details
Main Authors: Pu, Siyu, Hadinoto, Kunn
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2022
Subjects:
Online Access:https://hdl.handle.net/10356/163454
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-163454
record_format dspace
spelling sg-ntu-dr.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.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Engineering::Chemical engineering
Protein Crystallization
Crystal Shape
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
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.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Pu, Siyu
Hadinoto, Kunn
format Article
author Pu, Siyu
Hadinoto, Kunn
author_sort Pu, Siyu
title 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_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_sort salting-out crystallization of glycopeptide vancomycin: phase behavior study to control the crystal habit
publishDate 2022
url https://hdl.handle.net/10356/163454
_version_ 1753801133798719488