Obeticholic Acid Forms Two Series of Isostructural Non-stoichiometric Channel Solvates

The aim of this work was to investigate solid forms of an active pharmaceutical substance, obeticholic acid, and to characterize the discovered structures. Obeticholic acid is used to treat primary biliary cholangitis. No crystal structures have been published until now. Our X-ray powder diffraction results revealed that upon crystallization from various solvents, obeticholic acid forms one of two possible forms. Further investigation by thermogravimetric analysis and differential scanning calorimetry showed that the two forms are in fact solvated. Each solvate contains its respective solvent and, within the two series, the solvates are isostructural. The first series of solvates consists of n-butyl acetate, 2-butanone, n-heptane, and toluene solvates. The second series of solvates then contains isopropyl acetate, ethyl acetate, and tert-butyl-methyl ether solvates. Single-crystal X-ray diffraction showed that both solvate forms are channel solvates, in which the solvent occupies voids within the rigid obeticholic acid scaffold.