The external shape of crystalline particles (called morphology) is of paramount importance in a wide range of applications, in particular pharmaceuticals and pigments. In the production of pharmaceuticals, undesirable crystal morphologies such as needles and plates can cause serious problems in processing (e.g., slurry handling, filtration) and formulation (e.g., tableting, dissolution)
Crystal morphology can be controlled by careful selection of solvent mixtures and excipients (approved additives), although in practice this is done on a trial-and-error basis. In this project, we propose to use a combination of computational and experimental techniques to develop a rational approach to optimise the solvent mixture and to select optimal excipients for the crystallisation of drug particles with desired crystal morphology. The computational techniques involve the prediction of crystal morphology, the construction of major crystal growth surfaces, the study of the interaction of solvent and excipient molecules with these surfaces, and considering the impact of these interactions on the crystal morphology.
The experimental techniques involve standard crystallisation procedures using different combinations of solvents and excipients, and measuring the size and geometry of the resulting crystalline particles. As exemplar compounds, a few simple and easy to obtain compounds will be selected, such as aspirin, paracetamol, ibuprofen and quinacridone. Once the procedure has been developed and tested on these simple compounds, some more challenging substances will be selected. If the approach is successful, it can be commercialised.