LAPSE:2019.0968
Published Article
LAPSE:2019.0968
Direct Observation of Growth Rate Dispersion in the Enzymatic Reactive Crystallization of Ampicillin
August 15, 2019
Prediction and control of crystal size distributions, a prerequisite for production of consistent crystalline material in the pharmaceutical industry, requires knowledge of potential non-idealities of crystal growth. Ampicillin is one such medicine consumed in crystal form (ampicillin trihydrate). Typically it is assumed that all crystals of the same chemical and geometric type grow at the same rate, however a distribution of growth rates is often observed experimentally. In this study, ampicillin produced enzymatically is crystallized and a distribution of growth rates is observed as individual crystals are monitored by microscopy. Most studies of growth rate dispersion use complex flow apparatuses to maintain a constant supersaturation or imprecise measurements of size distributions to reconstruct growth rate dispersions. In this study, the controllable enzyme reaction enables the same information to be gathered from fewer, less complicated experiments. The growth rates of individual ampicillin trihydrate crystals were found to be normally distributed, with each crystal having an intrinsic growth rate that is constant in time. Differences in the individual crystals, such as different number and arrangement of dislocations and surface morphology, best explain the observed growth rates. There is a critical supersaturation below which growth is not observed, thought to be caused by reactants adsorbing to the crystal surface and pinning advancing growth steps. The distribution of critical supersaturation also suggests that individual crystals’ surface morphologies cause a distribution of growth rates.
Keywords
growth rate dispersion, penicillin G acylase, β-lactam antibiotics
Subject
Suggested Citation
McDonald MA, Bommarius AS, Grover MA, Rousseau RW. Direct Observation of Growth Rate Dispersion in the Enzymatic Reactive Crystallization of Ampicillin. (2019). LAPSE:2019.0968
Author Affiliations
McDonald MA: Georgia Institute of Technology, School of Chemical & Biomolecular Engineering, Atlanta, GA 30332, USA; Petit Institute for Bioengineering and Bioscience, Atlanta, GA 30332, USA [ORCID]
Bommarius AS: Georgia Institute of Technology, School of Chemical & Biomolecular Engineering, Atlanta, GA 30332, USA; Petit Institute for Bioengineering and Bioscience, Atlanta, GA 30332, USA; Georgia Institute of Technology, School of Chemistry and Biochemistry, Atlan [ORCID]
Grover MA: Georgia Institute of Technology, School of Chemical & Biomolecular Engineering, Atlanta, GA 30332, USA; Petit Institute for Bioengineering and Bioscience, Atlanta, GA 30332, USA [ORCID]
Rousseau RW: Georgia Institute of Technology, School of Chemical & Biomolecular Engineering, Atlanta, GA 30332, USA [ORCID]
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Journal Name
Processes
Volume
7
Issue
6
Article Number
E390
Year
2019
Publication Date
2019-06-22
Published Version
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr7060390, Publication Type: Journal Article
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LAPSE:2019.0968
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doi:10.3390/pr7060390
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Aug 15, 2019
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CC BY 4.0
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Aug 15, 2019
 
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Aug 15, 2019
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Original Submitter
Calvin Tsay
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