MS36-03 - Characterisation of “Polyamorphism” and the Molecular Origins of Disorder using Complementary Methods

Paul Hodgkinson (Durham University, United Kingdom)

Valsartan is a widely used antihypertensive drug marketed in an “amorphous” form. DSC studies show, however, that this form is distinct from a truly amorphous material produced by quench cooling from the melt. Powder diffraction and total scattering measurements show differences implying that the “as received” material has a greater degree of ordering, but neither material gives Bragg diffraction peaks. Counter-intuitively the more ordered material has a significantly higher solubility. Solid-state NMR is a powerful adjunct to diffraction-based techniques for the characterisation of pharmaceutical materials, particularly for characterising disorder. We used a combination of time-modulated DSC, PXRD and solid-state NMR to understand the molecular origin of this “polyamorphic” behaviour in terms of conformational “defects”[1]. Other examples are presented using co-crystals and solvates of pharmaceutical actives where quantum chemical calculations are invaluable in determining whether a disordered or an ordered structure is adopted[2,3]. Understanding why such disordered materials may be intrinsically stable is important in overcoming wariness about use of disordered materials as pharmaceutical forms.