Structural and thermal characterization of sodium ibandronate monohydrate Luciana Malpezzi • Elisabetta Maccaroni • Giordano Carcano • Gianpiero Ventimiglia Received: 22 September 2010 / Accepted: 24 May 2011 / Published online: 10 June 2011 Ó Akade ´miai Kiado ´, Budapest, Hungary 2011 Abstract Sodium Ibandronate (NaIb) belongs to the nitrogen-containing bisphosphonates drugs, used as anti- resorptive medications for the treatment of osteoporosis. The crystalline form of NaIb monohydrate was observed to undergo reversible thermal dehydration and rehydration, according to its hygroscopic nature and to the arrangement of the water molecules in the crystal lattice. Dehydration and rehydration were observed and confirmed by variable tem- perature X-ray diffraction on the basis of the DSC pattern and TG analysis that shows, by heating the sample from 40 to 200 °C, a loss of 5% weight corresponding to a water molecule loss. The water loss causes a phase transition to a more dense phase that can be rehydrated if it is left in a humid environment. The solid state characterization of NaIb monohydrate has been performed by X-ray single crystal diffraction analysis. The NaIb crystallizes as monohydrate salt in the triclinic system, space group P-1, with Z = 2, a = 5.973(1) A ˚ , b = 9.193(1) A ˚ , c = 14.830(2) A ˚ , a = 98.22(1)°, b = 98.97(1)°, c = 93.74(1)°, V = 792.9(2) A ˚ 3 . Each anionic group exist as zwitterionic entity with a total charge of -1. In the crystal packing, the octahedral coor- dination around the Na cations determines a centrosym- metric double chains structure elongated into the [100] direction. The water molecules are located inside the inter- chains cavities. Keywords Sodium ibandronate Á X-ray analysis Á Thermal analysis Á Structure determination Introduction Sodium Ibandronate (NaIb) [3-(N-methyl-N 0 -pentyl)- amino-1-hydroxypropane-1,1-diphosphonic acid monoso- dium salt] belongs to the nitrogen-containing bisphospho- nates, a class of drugs used in the prevention and treatment of osteoporosis and similar diseases, which has been subjected to many pharmacological [1–3] and structural studies [4–8], in order to explore the structural basis of their activity against bone diseases and against some parasite replication. The sodium salts of the bisphosphonates compound show a fur- ther interest due to their better solubility and bio-availability. The bone is a living dynamic structure which constantly undergoes a process of bone resorption (breakdown) and bone formation. When this process of remodelling, or bone turnover, removes more bone than it replaces, osteoporosis results, increasing the risk of fracture. The bisphosphonates, by virtue of their P–C–P backbone structure which acts as inhibitor of the destructive phase of bone turnover (resorption), are currently the most effective anti-resorptive medications. Their anti-resorptive potency is influenced by the chemical and three-dimensional structure of the side chain attached to the central carbon of the P–C–P backbone and the presence of a nitrogen-containing group, at a critical distance from the carbon atom, has been know to increase the strength of the drug [9]. Sodium Ibandronate, a nitrogen- containing bisphosphonate derivative characterized by an aliphatic tertiary amine side chain (see Scheme 1), directly L. Malpezzi (&) Á E. Maccaroni Department of Chemistry, Materials and Chemical Engineering ‘‘G. Natta’’, Via Mancinelli 7, 20131 Milano, Italy e-mail: luciana.malpezzi@polimi.it G. Carcano CNR-IENI—Sezione di Lecco, Corso Promessi Sposi 29, 23900 Lecco, Italy G. Ventimiglia Chemessentia srl—Chemo Group, Via Bovio 6, 28100 Novara, Italy 123 J Therm Anal Calorim (2012) 109:373–379 DOI 10.1007/s10973-011-1698-z