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Details of Grant 

EPSRC Reference: EP/Z533051/1
Title: Using microheterogeneous binary solvent systems for particle property control
Principal Investigator: Edkins, Professor K
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Inst of Pharmacy and Biomedical Sci
Organisation: University of Strathclyde
Scheme: Standard Research TFS
Starts: 01 July 2024 Ends: 30 September 2025 Value (£): 154,316
EPSRC Research Topic Classifications:
Chemical Biology
EPSRC Industrial Sector Classifications:
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Panel History:  
Summary on Grant Application Form
The control of solid materials is essential in the pharmaceutical manufacturing as it enables handling, purification and formulation. While the importance of controlling the crystal form is well-known since high-profile failures such as the ritonavir case, the impact of particle shape is less obvious to the non-specialist. The particle shape can be isotropic with near-equal dimensions leading to spherulites or blocks, or anisotropic in which one or two dimensions are larger than the remaining such as in needles or plates. Anisotropic particle shape reduces powder flow, leads to longer filtering times and higher solvent retention, and worsens tablet compaction. While currently particle shape is tackled on a small scale during the early development crystallisation or by a downstream grinding operation, neither is straightforward to scale up and both add time and cost to the development process. Therefore, a new approach allowing for scale-independent particle shape control would significantly speed up the development process.

In this project, we will investigate the impact of the microstructure of binary solvent mixtures on particle shape. Some binary solvent mixtures, such as acetonitrile/water, show a thermodynamic demixing on the microscale - a microheterogeneity. These mixtures lead to the spontaneous formation of droplets of one solvent in a matrix of the other, which generates confinement of crystallisation of drugs predominantly soluble in the droplets. We hypothesise that this confinement will limit the growth of the dominant growth axes. We will hence use the microheterogeneity to alter the macroscopic particle shape of highly anisotropic materials during the crystallisation process.

Furthermore, we will show that the developed method is scale and equipment independent. Since the microheterogeneity is a thermodynamic characteristic of a binary solvent mixture, the scale is irrelevant for its formation. We will hence show that our method can be scaled up from laboratory scale to pre-manufacturing scale of 20 litres. Furthermore, we will transfer the method between batch and continuous crystallisation equipment to prove that it can be directly implemented into the industrial development pathway.

This proof-of-concept study will revolutionise scale up of particle control by opening a completely novel pathway of particle shape control through a simple method based on a thermodynamic characteristic of the solvent mixture used without the need for additives or specialist equipment. This improvement especially in the robust scale-up potential will significantly reduce the time-to-market of new medicines, be it small molecule or new modalities, where particle shape can pose a major pain point. While we envisage the method's main impact to be in the pharmaceutical field, it will be translatable into any other industry where particle shape must be controlled.
Key Findings
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Organisation Website: http://www.strath.ac.uk