Structure of the active pharmaceutical ingredient bismuth subsalicylate

04 October 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


Structure determination of pharmaceutical compounds is invaluable for drug development but is challenging for those that form as small crystals with defects. Bismuth subsalicylate (BSS), among the most commercially significant bismuth compounds, is an active ingredient in over-the-counter medications such as Pepto-Bismol, used to treat dyspepsia and H. pylori infections. Despite its century-long history, the structure has remained unknown. Three-dimensional electron diffraction and hierarchical clustering analysis were applied on select data from ordered crystals, revealing a layered structure. In other less ordered crystals, high-resolution scanning transmission electron microscopy revealed variations in the stacking of layers. Together, these modern electron crystallography techniques provide a new toolbox for structure determination of active pharmaceutical ingredients and drug discovery, demonstrated by this study of BSS.


bismuth subsalicylate
electron diffraction
scanning transmission electron microscopy

Supplementary materials

Supplementary information
Materials and methods, supplemental figures and tables


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