Studying facet-specific incorporation of impurities during crystal growth of pharmaceutical materials
In the pharmaceutical industry, crystallisation is the most frequently used separation process in the manufacturing of solid particles. Apart from providing well-defined solid particles, it offers an inexpensive means of product purification. Typical pharmaceutical products are produced at purity levels ≥ 99.5% using crystallisation. However, the attainable purity depends strongly on the host/impurity system and is the result of kinetic and structural factors (e.g., solid solution formation). This often limits the effectiveness of crystallisation as a purification process. While the impact of impurities on crystallisation kinetics and the crystal shape is widely acknowledged, little has been done to link kinetics, molecular similarity, and surface chemistry to the molecular processes involved in impurity incorporation. Consequently, process design for enhanced purity is still performed using an empirical approach, often resulting in crystallization processes that are not necessarily as cost-efficient as they could be.
Crystals grow as well-ordered structures with faceted shapes related to the underlying symmetry of the crystal lattice. Each facet is a termination of the crystal structure and hence exposes a unique arrangement of host molecules and chemical functionalities to the environment. For different facets, this results in different growth rates and abilities to accept/reject impurities present in the solution. Impurity incorporation/rejection is therefore inherently surface-specific. While this is conceptually clear, a mechanistic and predictive understanding of this phenomenon has so far proved to be elusive.
A step change in process design capabilities for enhanced purity requires a molecular scale approach/understanding. Recent advances in surface analysis techniques make it timely and possible to investigate the impurity incorporation in a more precise fashion than ever before and to do so in a facet-specific manner. In this project, such detailed measurements will be obtained using a combination of surface-specific techniques, such as atomic force microscopy (including surface-enhanced and possibly tip-enhanced Raman spectroscopy (SERS, TERS), as well as X-ray photoelectron spectroscopy, XPS). The outcome of this research has the potential to enable “first-principles”-based design strategies for crystallization processes yielding high purity materials. This in turn, can open new and cheaper avenues towards highly pure pharmaceutical products.
The successful candidate will join the Crystal Chemistry and Particulate Process Engineering research group at the University of Manchester, School of Chemical Engineering and Analytical Science under the supervision of Dr Thomas Vetter. The advertised research project is part of a larger research initiative within the Royal Academy of Engineering research fellowship of Dr Vetter, so that the candidate can expect to part of a team working towards the above common goal with different simulation and experimental techniques.
The successful candidate will learn the fundamentals of crystal growth theory, gain experience in growing molecular crystals in the laboratory and track such crystal growth processes and learn how to use surface characterization techniques.
Applicants should have or expect to achieve at least a 2.1 honours degree in Chemical Engineering, Chemistry, Physics or a closely related subject.
Funding covers fees and stipend for UK/European students.
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FTE Category A staff submitted: 33.90
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