Solid State forms of Zoledronic Acid: polymorphism in hydrates

M. BIANCHI; M. RUSCICA; M. QUINTERO; A. MARTINEZ; D. VEGA

JOURNAL OF PHARMACEUTICAL SCIENCES

JOHN WILEY & SONS INC

Año: 2010 vol. 99 p. 4962 - 4972

0022-3549

Solid state forms of zoledronic acid, a nitrogen containing bisphosphonate used fortreatment of bone diseases, are studied using different experimental techniques (DSC,TG, XRD). Two degrees of hydration are obtained, containing one and three watermolecules per zoledronic acid molecule. The crystal structure of the trihydrated form isreported. Two different anhydrated forms are obtained when the hydrated ones wereheated. Besides, during the dehydration process, an amount of metastable amorphousphase appears, as a function of the dehydration rate. The stability of the obtainedcrystalline forms is examined under high humidity and a different trihydrated form wasobtained, setting clear that the same degree of hydration (trihydrated) can be obtained intwo different crystalline forms, and then very different thermal behavior is observed.