High-Throughput Co-Former Screening and Structural Elucidation Using Resonant Acoustic Mixing and 3D Electron Diffraction

Abstract

Integrating 3D Electron Diffraction (3D ED) analysis into the screening workflow of multicomponent systems facilitates direct structural determination from high-throughput Resonant Acoustic Mixing (RAM). This screening method enables the investigation of a wide experimental landscape, including various co-formers and solvents, within a short timeframe. Consequently, it allows for the rapid and efficient generation of numerous potential novel materials. Hit identification from the screening process is conducted through high-throughput X-Ray Powder Diffraction (XRPD) and Raman microscopy, followed by structural determination of selected novel phases by 3D ED. This workflow has been demonstrated using sulfasalazine as an example active pharmaceutical ingredient (API), encompassing a broad range of crystallisation conditions. Multiple distinct diffractograms were observed, leading to the discovery and structural characterisation of two novel multicomponent systems of sulfasalazine by 3D ED, one of which shows evidence of tautomerisation within a single crystal.