title: Investigating albendazole desmotropes by solid-state NMR spectroscopy.
abstract: Characterization of the molecular structure and physicochemical solid-state properties of the solid forms of pharmaceutical compounds is a key requirement for successful commercialization as potential active ingredients in drug products. These properties can ultimately have a critical effect on the solubility and bioavailability of the final drug product. Here, the desmotropy of Albendazole forms I and II was investigated at the atomic level. Ultrafast magic angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectroscopy, together with powder X-ray diffraction, thermal analysis, and Fourier transform infrared spectroscopy, were performed on polycrystalline samples of the two solids in order to fully characterize and distinguish the two forms. High-resolution one-dimensional (1)H, (13)C, and (15)N together with two-dimensional (1)H/(1)H single quantum-single quantum, (1)H/(1)H single quantum-double quantum, and (1)H/(13)C chemical shift correlation solid-state NMR experiments under MAS conditions were extensively used to decipher the intramolecular and intermolecular hydrogen bonding interactions present in both solid forms. These experiments enabled the unequivocal identification of the tautomers of each desmotrope. Our results also revealed that both solid forms may be described as dimeric structures, with different intermolecular hydrogen bonds connecting the tautomers in each dimer.
authors.affiliation: Facultad de Matemática, Astronomía y Física and IFEG (CONICET), Universidad Nacional de Córdoba , Ciudad Universitaria, X5000HUA Córdoba, Argentina.
authors.forename: Ana K
authors.initials: AK
authors.lastname: Chattah
authors.forename: Rongchun
authors.initials: R
authors.lastname: Zhang
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Mroue
authors.forename: Laura Y
authors.initials: LY
authors.lastname: Pfund
authors.forename: Marcela R
authors.initials: MR
authors.lastname: Longhi
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
authors.forename: Claudia
authors.initials: C
authors.lastname: Garnero
mesh_terms: D015766:Albendazole / Q000737:chemistry*; D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry; D001702:Biopharmaceutics; D019281:Dimerization; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D033362:Powder Diffraction; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000977:Antiparasitic Agents; D015766:Albendazole
keywords: RFDR; albendazole; characterization; desmotropy; solid-state NMR; tautomerism; ultrafast MAS