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From formulation to structure: 3D electron diffraction for the structure solution of a new indomethacin polymorph from an amorphous solid dispersion.
Leung, Helen W; Copley, Royston C B; Lampronti, Giulio I; Day, Sarah J; Saunders, Lucy K; Johnstone, Duncan N; Midgley, Paul A.
Afiliación
  • Leung HW; Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, United Kingdom.
  • Copley RCB; GSK R&D, Gunnels Wood Road, Stevenage SG1 2NY, United Kingdom.
  • Lampronti GI; Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, United Kingdom.
  • Day SJ; Beamline I11, Diamond Light Source, Didcot, Oxford OX11 0DE, United Kingdom.
  • Saunders LK; Beamline I11, Diamond Light Source, Didcot, Oxford OX11 0DE, United Kingdom.
  • Johnstone DN; GSK R&D, Gunnels Wood Road, Stevenage SG1 2NY, United Kingdom.
  • Midgley PA; Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, United Kingdom.
IUCrJ ; 11(Pt 5): 744-748, 2024 Sep 01.
Article en En | MEDLINE | ID: mdl-39194259
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IUCrJ Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IUCrJ Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Reino Unido