“Inconvenient Truths about Solid Form Landscapes”

The keynote speaker at our recent ‘Polymorphism and Crystallisation’ Conference in Boston was Dr Susan M. Reutzel-Edens from Eli Lilly, whose name will very familiar to anyone working in the solid form / crystallisation and she gave what one delegate described as “the best talk I have ever heard”. Now I can’t entirely agree with that delegate because I have seen Dr Reutzel-Edens talk several times before and every talk has been of a very high standard.

This particular presentation – “Inconvenient Truths about Solid Form Landscapes” covered a variety of examples from her experience at Eli Lilly in many cases molecules which did not behave in line with conventional thinking about solid forms, such as a compound which formed a stoichiometric dihydrate and a non-stoichiometric hydrate.  Conventional wisdom suggests the non-stoichiometric hydrate is probably a channel hydrate whilst the water in the dihydrate would be expected to be more tightly bound. So, the non-stoichiometric hydrate should be easier to dry but in fact quite the opposite was found to be the case. The non-stoichiometric hydrate appeared to have a somewhat flexible structure that would adapt to some loss of water meaning the remaining water became more tightly bound.

The other main area that was covered was crystal structure prediction and how sometimes the structures that are actually observed do appear to be the most stable forms when compared with the large number of predicted structures, but not always. As ever when studying crystal forms it is not just about thermodynamics, but also the kinetics of nucleation and crystal growth and also the relative stability of the required conformation in solution.