Promising drug candidates often fail to become marketed products, because the unfavourable physical properties of the drug prevent the development of effective formulations. Cocrystallisation, the formation of crystalline materials that combine the active ingredient with another molecule (called the coformer), has emerged recently as a strategy to influence the physical properties of solid drugs. Cocrystals have been shown to successfully address problems such as low solubility, hygroscopicity, poor crystallinity and low melting point. Currently no reliable methods exist for the prediction of cocrystal properties, so cocrystals with favourable properties are usually found through a trial-and-error procedure.
The aim of this project is to develop a strategy to predict and design the pharmaceutically relevant properties of cocrystals. We have found that the properties of cocrystals cannot be simply calculated from the corresponding properties of the drug and the coformer, although broad general trends can be identified. The project will investigate how intermolecular interactions and structural arrangements can be taken into account to explain deviations from the general trends. For example, formation of a complex between drug and coformer in solution is expected to have a significant effect on cocrystal solubility. A wide range of experimental techniques will be used to characterise cocrystals (X-ray diffraction, NMR, and IR spectroscopy, dissolution testing, differential scanning calorimetry). Interactions between drug and coformer molecules will be probed experimentally both in the solution and in the solid state by NMR spectroscopy and by X-ray diffraction. These methods give detailed and complementary information about intermolecular interactions and the structures of molecular assemblies. NMR reflects local structure and dynamics in both solutions and solids, while X-ray diffraction reveals the time-averaged long-range structure of crystalline materials. Information about the measured properties of cocrystals, the interactions between their molecules and the structures of the molecular assemblies involved in their formation will be collated to form predictive models. We will finally assess how much experimental data is needed for reliable predictions and to what extent computational models (force-field and quantum methods) can be used to substitute for experimental data.

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(ii) L. Fabian, N. Hamill, K. S. Eccles, H. A. Moynihan, A. R. Maguire, L. McCausland, S. E. Lawrence (2011). Cocrystals of Fenamic Acids with Nicotinamide. Crystal Growth & Design, 11, 3522-3528.
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