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Structural characterisation of amorphous solid dispersions via metropolis matrix factorisation of pair distribution function data.
Chem Commun (Camb) 2019; 55(89):13346-13349CC

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 via its 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.

Authors+Show Affiliations

Department of Chemistry, University of Oxford, Inorganic Chemistry Laboratory, South Parks Road, Oxford OX1 3QR, UK. andrew.goodwin@chem.ox.ac.uk.Pharmaceutical Development, AstraZeneca, Macclesfield, SK10 2NA, UK.Pharmaceutical Development, AstraZeneca, Macclesfield, SK10 2NA, UK.Pharmaceutical Development, AstraZeneca, Macclesfield, SK10 2NA, UK.Department of Chemistry, University of Oxford, Inorganic Chemistry Laboratory, South Parks Road, Oxford OX1 3QR, UK. andrew.goodwin@chem.ox.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31580357

Citation

Geddes, Harry S., et al. "Structural Characterisation of Amorphous Solid Dispersions Via Metropolis Matrix Factorisation of Pair Distribution Function Data." Chemical Communications (Cambridge, England), vol. 55, no. 89, 2019, pp. 13346-13349.
Geddes HS, Blade H, McCabe JF, et al. Structural characterisation of amorphous solid dispersions via metropolis matrix factorisation of pair distribution function data. Chem Commun (Camb). 2019;55(89):13346-13349.
Geddes, H. S., Blade, H., McCabe, J. F., Hughes, L. P., & Goodwin, A. L. (2019). Structural characterisation of amorphous solid dispersions via metropolis matrix factorisation of pair distribution function data. Chemical Communications (Cambridge, England), 55(89), pp. 13346-13349. doi:10.1039/c9cc06753a.
Geddes HS, et al. Structural Characterisation of Amorphous Solid Dispersions Via Metropolis Matrix Factorisation of Pair Distribution Function Data. Chem Commun (Camb). 2019 Nov 18;55(89):13346-13349. PubMed PMID: 31580357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural characterisation of amorphous solid dispersions via metropolis matrix factorisation of pair distribution function data. AU - Geddes,Harry S, AU - Blade,Helen, AU - McCabe,James F, AU - Hughes,Leslie P, AU - Goodwin,Andrew L, Y1 - 2019/10/03/ PY - 2019/10/4/pubmed PY - 2019/10/4/medline PY - 2019/10/4/entrez SP - 13346 EP - 13349 JF - Chemical communications (Cambridge, England) JO - Chem. Commun. (Camb.) VL - 55 IS - 89 N2 - 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 via its 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. SN - 1364-548X UR - https://www.unboundmedicine.com/medline/citation/31580357/Structural_characterisation_of_amorphous_solid_dispersions_via_metropolis_matrix_factorisation_of_pair_distribution_function_data L2 - https://doi.org/10.1039/c9cc06753a DB - PRIME DP - Unbound Medicine ER -