From formulation to structure: 3D electron diffraction for the structure solution of a new indomethacin polymorph from an amorphous solid dispersion

3D electron diffraction (3DED) is increasingly employed to determine molecular and crystal structures from micro-crystals. Indomethacin is a well known, marketed, small-molecule non-steroidal anti-inflammatory drug with eight known polymorphic forms, of which four structures have been elucidated to...

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Bibliographic Details
Published in:IUCrJ 2024-09, Vol.11 (5), p.744-748
Main Authors: Leung, Helen W, Copley, Royston C B, Lampronti, Giulio I, Day, Sarah J, Saunders, Lucy K, Johnstone, Duncan N, Midgley, Paul A
Format: Article
Language:English
Subjects:
3d electron diffraction
active pharmaceutical ingredients
amorphous solid dispersions
drug development
indomethacin
pharmaceutical formulation
polymorphism
structure determination
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Summary:3D electron diffraction (3DED) is increasingly employed to determine molecular and crystal structures from micro-crystals. Indomethacin is a well known, marketed, small-molecule non-steroidal anti-inflammatory drug with eight known polymorphic forms, of which four structures have been elucidated to date. Using 3DED, we determined the structure of a new ninth polymorph, σ, found within an amorphous solid dispersion, a product formulation sometimes used for active pharmaceutical ingredients with poor aqueous solubility. Subsequently, we found that σ indomethacin can be produced from direct solvent evaporation using dichloromethane. These results demonstrate the relevance of 3DED within drug development to directly probe product formulations.
ISSN:2052-2525
2052-2525
DOI:10.1107/S2052252524008121