Structure of the active pharmaceutical ingredient bismuth subsalicylate

Structure determination of pharmaceutical compounds is invaluable for drug development but is challenging for materials 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 (genericized trademark), 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 less ordered crystals high-resolution scanning transmission electron microscopy revealed various disorders, including variations in the stacking of layers. These modern electron crystallography techniques provide insight into differences in BSS crystals and the possibility to develop new analogs or polymorphs.