Kaskiewicz, PL orcid.org/0000-0001-6708-6687, Xu, G, Lai, X et al. (5 more authors) (2019) Isothermal by Design: An Accelerated Approach to the Prediction of the Crystallizability of Slowly Nucleating Systems. Organic Process Research and Development, 23 (9). pp. 1948-1959. ISSN 1083-6160
Abstract
A route to the accelerated nucleation of α-para-aminobenzoic acid in ethanol/water (EtOH/H2O) mixed solvent solutions, using antisolvent crystallization, is presented. An isothermal by design approach is adopted, whereby the exothermic enthalpy of mixing associated with antisolvent addition is offset by the control of the temperature of the antisolvent added. Induction times (τ) are found to be reduced by 4 orders of magnitude using this methodology, consistent with the use of this approach as a nucleation acceleration technique. Calculation of the nucleation kinetic parameters for a range of solution concentrations, compositions, and supersaturations (S) reveal that effective interfacial tensions (γeff) vary from 8.4 to 2.3 mJ m–2 from solutions in H2O solvent and EtOH solvent, respectively, in line with the trend in solubility. The critical nucleus radius (r*) decreases from 1.98 to 0.40 nm associated with a decrease in the number of molecules in the critical nucleus (i*) from 196 to 2 molecules. A change in nucleation mechanism from heterogeneous nucleation to homogeneous nucleation is observed to take place at S ≈ 1.5. Limitations, particularly with focus toward larger-scale operation, are highlighted together with potential solutions to overcome such aspects.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019, American Chemical Society. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | crystallization; nucleation; induction time; antisolvent; drown out; stability; kinetics; para-aminobenzoic acid |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemical & Process Engineering (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Oct 2019 12:21 |
Last Modified: | 25 Jun 2023 22:00 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/acs.oprd.9b00242 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:151708 |