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.

1. M. Skotnicki, D. C. Apperley, J. A. Aguilar, B. Milanowski, M. Pyda and P. Hodgkinson, Mol. Pharmaceutics 13 (2016) 13

2. H. E. Kerr, H. E. Mason, H. A. Sparkes and P. Hodgkinson, CrystEngComm 18 (2016) 6700

3. A. Bērziņš and P. Hodgkinson, Solid State Nucl. Magn, Reson. 65 (2015) 12