Nappo, Valentina;
(2018)
Experimental study on the influence of fluid dynamics and mixing on crystallisation of PABA in multiphase flow systems.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Cooling crystallization is extensively used by the pharmaceutical industry to produce and purify Active Pharmaceutical Ingredients. Nucleation, that is the first step of crystallization, is pivotal in determining the final product properties. For these reasons, understanding the nucleation process and the factors that control crystal formation is essential to limit product variations and ultimately to improve the efficacy and the safety of the final drug. This thesis aims to investigate the mechanisms responsible for initiating nucleation in a clear solution and to identify the key process parameters that control nucleation. In particular, we used three experimental systems to explore the influence of micromixing, shear rate and gas bubbles under a wide range of fluid dynamic conditions. The first part of this work focuses on the experimental characterization of two laboratory scale batch systems to explore the effect of micromixing on metastable zone width (MZW) in industrial-like fluid dynamic conditions. The results demonstrated that, although increasing agitation is beneficial in reducing the MZW, the presence of gas bubbles was more effective in inducing nucleation supporting the theory that the gas bubbles offer a surface for heterogeneous nucleation. However, due to the complexity of the systems studied (non-spatially uniform fluid dynamic), it is difficult to untangle the effect of the various process parameters. For this reason, a novel droplet-based crystalliser was used to quantitatively investigate the effect of shear rate in well-controlled fluid dynamic conditions (quiescent-stagnant conditions, low-shear laminar flow and high-shear turbulent flow). The results suggested that a shear field can significantly enhance primary nucleation by increasing the meso-scale cluster collision efficiency. However, further experimentation is necessary in order to verify this hypothesis. Finally, a novel experimental system was proposed to explore the possibility of heterogeneous nucleation on gas bubbles. The experiments revealed that nucleation on gas-liquid interface is favoured.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Experimental study on the influence of fluid dynamics and mixing on crystallisation of PABA in multiphase flow systems |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10055690 |
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