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

21 August 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

pair distribution function
non-negative matrix facrtorisation
amorphous pharmaceuticals

Supplementary materials

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chemrxiv 2019 mmf
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