These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
2 files

Structural Characterisation of Amorphous Solid Dispersions via Metropolis Matrix Factorisation of Pair Distribution Function Data

submitted on 20.08.2019, 18:50 and posted on 21.08.2019, 18:12 by Harry Geddes, Helen Blade, James McCabe, Leslie P. Hughes, Andrew Goodwin
We measure the X-ray pair distribution functions (PDFs) of a series of felodipine:copovidone amorphous solid dispersions. Using a newly-developed Metropolis Matrix Factorisation (MMF) algorithm we extract from these data the PDF of the amorphous felodipine component in isolation. Our MMF analysis allows quantification of the degree of drug crystallinity in each sample, and structural characterisation of the amorphous drug viaits PDF. Comparison with atomistic simulations reveals that the (in)accessibility of conformational rotamers distinguishes amorphous and crystalline felodipine, in turn suggesting design routes for stabilising the amorphous form. We discuss the conceptual importance of our results in the context of characterising not only amorphous pharmaceuticals, but complex mixtures in general.


European Research Council 788144

European Research Council 279705

EPSRC studentship


Email Address of Submitting Author


University of Oxford



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest