From Formulation to Structure: 3D Electron Diffraction for the Structure Solution of a New Indomethacin Polymorph from an Amorphous Solid Dispersion

Overview

Journal IUCrJ

Date 2024 Aug 28

PMID 39194259

Authors

Helen W Leung

Royston C B Copley

Giulio I Lampronti

Sarah J Day

Lucy K Saunders

Duncan N Johnstone

Paul A Midgley

Affiliations

Soon will be listed here.

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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