IN-SITU structure solution and phase tranformation studies of drug polymorphs using high resolution synchrotron powder diffraction

W I F David and K Shankland

ISIS Facility, Rutherford Appleton Laboratory, Chilton, Oxfordshire, OX11 0QX, UK (Bill.David@rl.ac.uk)

With third generation synchrotron powder diffractometers, it is possible to collect high resolution diffraction patterns on 50-100 atom structures in a matter of minutes. This enables the rapid scanning of temperature to monitor structural phase transformations and search for new drug polymorphs. We show that it is possible to study the effects of dehydration and to discover new polymorphic forms as a matter of routine. The technique is essentially the structural equivalent of a combination of differential scanning calorimetry and thermo-gravimetric analysis. Three examples will be illustrated that show (i) the subtle effects that occur with the transformation from a hemihydrate to an anhydrous form, (ii) the detailed characterisation of a drug polymorphic phase transformation and (iii) the discovery and crystal structure solution of a new crystal polymorph.