Postgraduate research opportunities Exploiting Microheterogeneity in solvent systems for form and particle control

Crystallisation is one of the most common unit operations in the chemical industry, and is used to generate final materials with controlled crystal form and particle shape. But to control the crystallisation outcome throughout the scaling up process in difficult at best. In this project we will investigate the impact of microheterogeneity in solvent mixtures on the crystallisation outcome. Microheterogeneity forms when two or more solvents phase-separate on the microscopic scale. This thermodynamic property should be stable as long as we stay within the appropriate region of the phase diagram, and effects based on microheterogeneity can be exploited at various scales without change of structure.

The project runs in close collaboration with AstraZeneca as industrial partner and will look at the impact of microheterogeneity on:

1. crystal form: Does the phase separation have an impact on the crystallisation outcome, can we use it to inhibit certain crystal forms or ensure the appearance of others
2. particle characteristics: Can we influence the particle surface and shape with the microheterogeneity and change their flow characteristics, hygroscopicity, electrostatic behaviour, tablettability etc.?

We will use model compounds from the pharmaceutical field in the first place and move to industry-relevant compounds as proof of concept. We will also move the method into model scale-up to show industry applicability.

The successful candidate will work with a range of crystallization techniques and analyse the resulting materials with state-of-the art methods, ranging from FTIR and NMR spectroscopy to thermal analysis and diffraction methods. In addition, we will use neutron scattering on the microheterogeneous samples and combine this with computation modelling to get a structural model. Through the close collaboration with AstraZeneca, the successful candidate will be trained in all industry-relevant techniques as well as generate a close link to pharmaceutical industry for their further career.

Training

Training will be provided in:

• Crystallization and relevant thermodynamics
• Solid-state analytics including vibrational spectroscopy, diffraction and thermal analysis
• Molecular modelling
• Neutron scattering (small angle scattering and amorphous diffraction)
• Industry-relevant crystallization at various scales
• Soft skill relevant to the industrial and academic sector including presentation, writing and communication skills and career development