Thesis
Intensification of a workflow for particle engineering and crystallisation process development
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2024
- Thesis identifier
- T16979
- Person Identifier (Local)
- 202088128
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Crystallisation is a fundamental aspect of chemical and pharmaceutical manufacturing to ensure high purity, bio-availability and desirable physical attributes of quality products. In this thesis, a comprehensive workflow was designed to enhance the efficiency of crystallisation process development through the utilisation of digital tools. This research aims to integrate existing knowledge in crystallisation thermodynamics and kinetics and quality by design (QbD) principles into a unified framework. To develop and test the workflow’s approach, two case studies were conducted involving the crystallisation of lamivudine and aspirin. These studies served as foundational experiments to first develop the workflow and second validate the individual components and the logical flow of the workflow. Data collected was inclusive of solubility, morphological characteristics, particle size, kinetic properties, and solid forms in a time and material-reductive way. The two case studies highlighted a need for a more intelligent experimental planning and optimisation tool, particularly when contrasted with conventional methodologies. To address this requirement, an Adaptive Bayesian Optimisation (AdBO) tool was developed and applied to the crystallisation processes of lamivudine and aspirin. This acceleration of the workflow demonstrated significant advantages when compared to traditional grid search and design of experiment (DoE) optimisation approaches. Subsequently, the generalisability of the workflow was validated by applying it to five additional active pharmaceutical ingredient (API) case studies, ibuprofen, ascorbic acid, salicylic acid, benzoic acid and D-mannitol. This evaluation, across a broader chemical scope, demonstrated the versatility and robustness of the workflows approach. In contrast to conventional industrial research and development methods, which typically operate on a scale exceeding 100 mL, consume substantial time resources, and necessitate a large workforce, our workflow was integrated into an industrial pharmaceutical facility. This integration enabled the systematic validation of the workflow across various stirring methods, crystallisation modes, and vessel sizes, ultimately leading to the design of a robust hybrid antisolvent-cooling crystallisation process. This thesis provides a comprehensive framework for the optimisation of crystallisation processes, leveraging digital tools to streamline experimentation, enhance efficiency and promote consistency. This is impactful to the wider community as the workflow and digital tools developed can seamlessly be integrated into existing chemical and pharmaceutical research to yield efficiencies. The generalisability shown by this work also allows for the expansion of similar work packages into areas outside of chemical and pharmaceutical manufacturing.
- Advisor / supervisor
- Florence, Alastair
- Brown, Cameron
- Mustoe, Chantal
- Resource Type
- DOI
Beziehungen
Objekte
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PDF of thesis T16979 | 2024-07-03 | Öffentlich | Herunterladen |