Pal, S;
Pankajakshan, A;
Besenhard, MO;
Snead, N;
Almeida, J;
Abukhamees, S;
Craig, D;
... Mazzei, L; + view all
(2024)
Automated Continuous Crystallization Platform with Real-Time Particle Size Analysis via Laser Diffraction.
Organic Process Research and Development
, 28
(7)
pp. 2755-2764.
10.1021/acs.oprd.4c00110.
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Abstract
The fourth industrial revolution is gaining momentum in the pharmaceutical industry. However, particulate processes and suspension handling remain big challenges for automation and the implementation of real-time particle size analysis. Moreover, the development of antisolvent crystallization processes is often limited by the associated time-intensive experimental screenings. This work demonstrates a fully automated modular crystallization platform that overcomes these bottlenecks. The system combines automated crystallization, sample preparation, and immediate crystal size analysis via online laser diffraction (LD) and provides a technology for rapidly screening crystallization process parameters and crystallizer design spaces with minimal experimental effort. During the LD measurements, to avoid multiple scattering events, crystal suspension samples are diluted automatically. Multiple software tools, i.e., LabVIEW, Python, and PharmaMV, and logic algorithms are integrated in the platform to facilitate automated control of all the sensors and equipment, enabling fully automated operation. A customized graphical user interface is provided to operate the crystallization platform automatically and to visualize the measured crystal size and the crystal size distribution of the suspension. Antisolvent crystallization of ibuprofen, with ethanol as solvent and water with Soluplus (an additive) as antisolvent, is used as a case study. The platform is demonstrated for antisolvent crystallization of small ibuprofen crystals in a confined impinging jet crystallizer, performing automated preplanned user-defined experiments with online LD analysis.
| Type: | Article |
|---|---|
| Title: | Automated Continuous Crystallization Platform with Real-Time Particle Size Analysis via Laser Diffraction |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.oprd.4c00110 |
| Publisher version: | http://dx.doi.org/10.1021/acs.oprd.4c00110 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Antisolvent crystallization, automation, ibuprofen, process analytical technology, automated laser diffraction, online, LabVIEW, PharmaMV |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10195052 |
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