Journal article
Direct Observation of Growth Rate Dispersion in the Enzymatic Reactive Crystallization of Ampicillin
Processes, v 7(6), p390
01 Jun 2019
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Abstract
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.
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Details
- Title
- Direct Observation of Growth Rate Dispersion in the Enzymatic Reactive Crystallization of Ampicillin
- Creators
- Matthew A. McDonald - Georgia Institute of TechnologyAndreas S. Bommarius - Georgia Institute of TechnologyMartha A. Grover - Georgia Institute of TechnologyRonald W. Rousseau - Georgia Institute of Technology
- Publication Details
- Processes, v 7(6), p390
- Publisher
- Mdpi
- Number of pages
- 17
- Grant note
- 1540017 / NSF/IUCRC Center for Pharmaceutical Development U01FD006484 / FDA Center for Drug Evaluation and Research Georgia Institute of Technology's Specialty Separations Center ECCS-1542174 / National Science Foundation; National Science Foundation (NSF)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000475306200074
- Scopus ID
- 2-s2.0-85069961843
- Other Identifier
- 991021958008804721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Engineering, Chemical