MicroED and 3D Electron Diffraction: Pharmaceutical Literature, 2018–2026
Selected MicroED and 3D electron diffraction publications on pharmaceutical crystal structures, polymorphs, salts, cocrystals, solvates, drug products, and absolute configuration.
Selected for pharmaceutical relevance, methodological contribution, industrial evidence, and review value. This is an editorial collection, not a citation-count ranking or an exhaustive bibliography. Foundational 2018 studies are included.
Iryna Andrusenko; Victoria Hamilton; Arianna E. Lanza et al. International Journal of Pharmaceutics · DOI 10.1016/j.ijpharm.2021.121067
Researchers solved a previously unresolved indomethacin form by three-dimensional electron diffraction and related its packing to infrared and Raman observations. They measured faster dissolution than the better-characterized alpha and gamma forms and observed a solid-state transition to alpha. This is a solid-form structure–property study; laboratory dissolution results do not by themselves establish improved human bioavailability.
Why it is included: API structure–property case with dissolution and phase-transition measurements.
Molly Lightowler; Shuting Li; Xiao Ou et al. Angewandte Chemie International Edition · DOI 10.1002/anie.202114985
Three-dimensional electron diffraction showed that solution-grown and melt-grown materials previously grouped as delta-indomethacin have different crystal structures. The authors retained delta for the solution-grown form and proposed theta for the melt-grown form. Both displayed plastic bending associated with molecular slip. This case demonstrates how structural measurements can resolve longstanding ambiguity in polymorph identity.
Why it is included: Corrects a decades-old ambiguity in an extensively studied pharmaceutical polymorph system.
Helen W. Leung; Royston C. B. Copley; Giulio I. Lampronti; Sarah J. Day; Lucy K. Saunders; Duncan N. Johnstone; Paul A. Midgley IUCrJ · DOI 10.1107/s2052252524008121
3D electron diffraction resolved the structure of the ninth reported indomethacin polymorph, designated sigma, from crystals found within an amorphous solid dispersion. Subsequent experiments produced the same form by solvent evaporation. The work demonstrates structure determination directly from a formulation-related sample containing an excipient; it does not establish improved dissolution or clinical performance for the new form.
Why it is included: A highly relevant formulation case linking unexpected crystallinity in an ASD with definitive structure determination and a follow-up crystallization route.
Hidetomo Yokoo; Tatsuo Koide; Tamaki Miyazaki; Yoshitaka Aoyama; Yutaro Ogaeri; Eiichi Yamamoto; Yosuke Demizu; Nahoko Uchiyama Chemical and Pharmaceutical Bulletin · DOI 10.1248/cpb.c25-00377
This study characterized indomethacin–nicotinamide cocrystals using MicroED together with solid-state NMR, Raman spectroscopy, and powder X-ray diffraction. MicroED supplied the crystal structure, while NMR helped examine molecular interactions. The combined approach addressed properties that individual methods could not establish alone, offering a pharmaceutical cocrystal workflow relevant to API powders and formulations containing excipients.
Why it is included: A concrete cocrystal example showing how electron diffraction and spectroscopic evidence can complement each other in pharmaceutical structural characterization.
