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

Autor:	Helen W. Leung, Royston C. B. Copley, Giulio I. Lampronti, Sarah J. Day, Lucy K. Saunders, Duncan N. Johnstone, Paul A. Midgley
Jazyk:	angličtina
Rok vydání:	2024
Předmět:	indomethacin amorphous solid dispersions drug development 3d electron diffraction polymorphism structure determination pharmaceutical formulation active pharmaceutical ingredients Crystallography QD901-999
Zdroj:	IUCrJ, Vol 11, Iss 5, Pp 744-748 (2024)
Druh dokumentu:	article
ISSN:	2052-2525 20522525
DOI:	10.1107/S2052252524008121
Popis:	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.
Databáze:	Directory of Open Access Journals
Externí odkaz:	https://doaj.org/article/4b8a69304af1467b8773d3c4b670d968 Zobrazit plný text záznamu View record in DOAJ