The solution interaction of diatrizoic acid with water towards hydrate formation

The incorporation of water into crystalline materials leads to significant problems in pharmaceutical formulation, as these materials show thermodynamically the lowest solubility in water leading to reduced bioavailability and potential inefficiency of the medicine. We are working on determining the interactions between solute and water in the pre-crystallisation solution with the aim to predict hydrate formation before the crystallisation experiment. We have recently worked on diatrizoic acid, an X-ray contrast agent that forms a highly stable dihydrate, and collected neutron total scattering data on the compound in DMSO solution with six equivalents of water. While the found interactions are not strong enough to warrant hydrate formation, we also discovered that the dihydrate does not crystallise from these solutions - they yield previously unknown crystal forms. We now propose to determine the solution structure of diatrizoic acid in DMSO:water 1:1 mixtures, from which the dihydrate does crystallise. With this data, we can determine the interaction characteristics needed for hydrate formation to occur, and why this material does not result from lower water contents.