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

preprint
submitted on 20.08.2019 and posted on 21.08.2019 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.

Funding

European Research Council 788144

European Research Council 279705

EPSRC studentship

History

Email Address of Submitting Author

andrew.goodwin@chem.ox.ac.uk

Institution

University of Oxford

Country

UK

ORCID For Submitting Author

0000-0001-9231-3749

Declaration of Conflict of Interest

No conflict of interest

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