Structural and thermal characterization of zolpidem hemitartrate hemihydrate (Form E) and its decomposition products by laboratory X-ray powder diffraction.
The crystal structure of zolpidem hemitartrate hemihydrate (I, Form E) has been solved from high-resolution laboratory powder diffraction data. It crystallizes in the orthorhombic P2(1)2(1)2(1) space group with a = 22.4664(6) A, b = 26.0420(7) A, and c = 7.4391(1) A. Protonation of zolpidem molecules could not be unambiguously determined. Thermal stability of Form E has been investigated by TG-DTA and in situ by temperature resolved X-ray powder diffraction. Water loss occurs between 50 degrees C <or= t <or= 100 degrees C while structure decomposition commences at approximately 120 degrees C yielding zolpidem tartrate (II) and pure zolpidem base (III) in approximately equimolar amounts. Crystal structures of II and III have been solved simultaneously from a single powder pattern of thermally decomposed I. Zolpidem tartrate crystallizes in the orthorhombic P2(1)2(1)2(1) space group with a = 19.9278(8) A, b = 15.1345(8) A, and c = 7.6246(2) A (at 140 degrees C). Zolpidem base crystallizes in the orthorhombic Pcab space group with a = 9.9296(4) A, b = 18.4412(9) A, and c = 18.6807(9) A (at 140 degrees C). In the reported crystal structures zolpidem molecules form stacks through pi-pi interaction or dipole-dipole interactions while tartrate moieties, if present, form hydrogen bonded chains. Water molecule in I forms a hydrogen bond to the imidazole nitrogen atom of the zolpidem molecule. Free space in the crystal structure of I could allow for the additional water molecules and thus a variable water content.
Halasz
Ivan
I
Max-Planck Institute for Solid State Research, Stuttgart, Germany. i.halasz@fkf.mpg.de
Dinnebier
Robert E
RE
D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D006860:Hydrogen Bonding; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D015233:Models, Statistical; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D012997:Solvents; D013696:Temperature; D013816:Thermodynamics; D014961:X-Ray Diffraction; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011725:Pyridines; D012997:Solvents; D000077334:Zolpidem