title: Aging-driven decomposition in zolpidem hemitartrate hemihydrate and the single-crystal structure of its decomposition products.
abstract: The "aging-driven" decomposition of zolpidem hemitartrate hemihydrate (form A) has been followed by X-ray powder diffraction (XRPD), and the crystal and molecular structures of the decomposition products studied by single-crystal methods. The process is very similar to the "thermally driven" one, recently described in the literature for form E (Halasz and Dinnebier. 2010. J Pharm Sci 99(2): 871-874), resulting in a two-phase system: the neutral free base (common to both decomposition processes) and, in the present case, a novel zolpidem tartrate monohydrate, unique to the "aging-driven" decomposition. Our room-temperature single-crystal analysis gives for the free base comparable results as the high-temperature XRPD ones already reported by Halasz and Dinnebier: orthorhombic, Pcba, a = 9.6360(10) Å, b = 18.2690(5) Å, c = 18.4980(11) Å, and V = 3256.4(4) Å(3) . The unreported zolpidem tartrate monohydrate instead crystallizes in monoclinic P21 , which, for comparison purposes, we treated in the nonstandard setting P1121 with a = 20.7582(9) Å, b = 15.2331(5) Å, c = 7.2420(2) Å, γ = 90.826(2)°, and V = 2289.73(14) Å(3) . The structure presents two complete moieties in the asymmetric unit (z = 4, z' = 2). The different phases obtained in both decompositions are readily explained, considering the diverse genesis of both processes.
authors.affiliation: Grupo Materia Condensada, GIyA, GAIyANN, CAC, Comisión Nacional de Energía Atómica, Av. Gral. Paz 1499, (1650) San Martín, Buenos Aires, Argentina; Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, Buenos Aires, Argentina. vega@cnea.gov.ar.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Vega
authors.forename: Ricardo
authors.initials: R
authors.lastname: Baggio
authors.forename: Mariana
authors.initials: M
authors.lastname: Roca
authors.forename: Dora
authors.initials: D
authors.lastname: Tombari
mesh_terms: D004355:Drug Stability; D058785:GABA-A Receptor Agonists / Q000737:chemistry*; D006993:Hypnotics and Sedatives / Q000737:chemistry*; D008958:Models, Molecular; D033362:Powder Diffraction; D011725:Pyridines / Q000737:chemistry*; D014961:X-Ray Diffraction; D000077334:Zolpidem
chemical_list: D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem