Characterization of the structure of amorphous disodium etidronate

Disodium ethane-1-hydroxy-1,1-bisphosphonate (disodium etidronate) is a first-generation bisphosphonate that is widely used in treating osteoporosis and Paget’s disease. Pharmaceuticals prepared using disodium etidronate as the drug substance have a crystalline form. Compared with crystalline formulations, amorphous formulations exhibit higher water solubility. However, stable amorphization has not yet been achieved, and clarification of its structural origin is still needed. In this study, high-energy X-ray diffraction and reverse Monte Carlo structural modeling were performed to determine the static structures of amorphous compounds. Na ions have to be placed both within and outside the molecules, such as between phosphate and hydroxyl groups and outside the phosphate groups, respectively, to reproduce the structural factors contributing to amorphization.