Solid-state forms of zoledronic acid: polymorphism in hydrates.

Solid-state forms of zoledronic acid, a nitrogen-containing bisphosphonate used for treatment of bone diseases are studied using different experimental techniques (DSC, TG, and XRD). Two degrees of hydration have been obtained, containing one and three water molecules per zoledronic acid molecule. The crystal structure of the trihydrated form is reported. Two different anhydrated forms have been obtained when the hydrated ones were heated. Besides, during the dehydration process, an amount of metastable amorphous phase appears, as a function of the dehydration rate. The stability of the obtained crystalline forms is examined under high humidity and a different trihydrated form was obtained, setting clear that the same degree of hydration (trihydrated) can be obtained in two different crystalline forms, and then very different thermal behaviors have been observed.