Salt and cocrystal former selection to obtain well-behaved crystalline solid forms

PhD Studentship in Solid-State Pharmaceutical Chemistry and Structural Informatics


University of East Anglia in collaboration with the Cambridge Crystallographic Data Centre


Project: Salt and cocrystal former selection to obtain well-behaved crystalline solid forms

Supervisors: Dr László Fábián (UEA), Dr Neil Feeder (CCDC).

This 3 year PhD research project, due to start in Oct 2013, is a collaboration between the University of East Anglia (UEA, School of Pharmacy) and the Cambridge Crystallographic Data Centre (CCDC), a University Partner Institute of the University of Cambridge (www.ccdc.cam.ac.uk). The doctoral student will be based at UEA, but will spend some of their time in Cambridge. Full funding for 3 years is available for UK/EU students only.

Solid dosage forms, such as tablets and capsules are the most common vehicles for administering medicines. The advantages of solid dosage forms include their relative ease of handling and manufacture, stability, reliable dosing and patient convenience. Unfortunately, current drug discovery techniques often identify large, complex molecules as drug candidates. The complexity and conformational flexibility of these molecules mean that obtaining stable crystalline solids from them is often very difficult. Salts and cocrystals incorporate a counterion or a neutral molecule into their crystals along with the active ingredient, which, if selected carefully, can stabilise the resulting solid. This careful selection of co-formers is still largely based on trial-and-error, and there are no rules to predict which co-former will form a stable crystal with a particular drug.

The aim of the project is to develop a knowledge-based strategy for the selection of counterions and co-crystal formers that are most likely to produce solids with high crystallinity and low hygroscopicity. For this we need to understand the essential mechanisms through which multi-component crystals provide stable crystalline solids. The complex interplay of many factors means that individual experiments provide little insight. Consequently, a statistical, data mining approach is required. The Cambridge Structural Database (CSD), which contains over 600,000 crystal structures, provides the large body of experimental data required. The focus of the project will be the creative use and adaptation of existing cheminformatics and data mining tools to extract information on stable association patterns between the molecules of multi-component crystals, to interpret this information in chemical and structural terms, and to use this information predictively in counterion and co-former selection.

The studentship offers the opportunity for a gifted individual to work on a problem of great practical significance, supported by two scientific groups at the forefront of structural informatics. The candidate should have a first or upper second BSc/MSc/MPharm degree in chemistry, pharmacy, computer science or a similar discipline. Familiarity with molecular modelling, chemical information systems, crystallography or computer programming would be useful additional experience. The successful candidate will gain experience in a wide variety of chemical informatics and modelling methods, database searching tools, and statistical analysis methodology in a discipline which is of direct relevance to the pharmaceutical and chemical industries.

Please apply online via the following link:
http://www.uea.ac.uk/study/postgraduate/research-degrees/science/pharmacy. For informal enquiries contact Dr László Fábián ([Email Address Removed]). The deadline for applications is the 31st May. To be eligible for a full award, applicants must satisfy UK or EU residency criteria.