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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 P212121 space group with a = 22.4664(6) Å, b = 26.0420(7) Å, and c = 7.4391(1) Å. 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 °C to 100 °C while structure decomposition commences at approximately 120 °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 P212121 space group with a = 19.9278(8) Å, b = 15.1345(8) Å, and c = 7.6246(2) Å (at 140°C). Zolpidem base crystallizes in the orthorhombic Pcab space group with a = 9.9296(4) Å, b = 18.4412(9) Å, and c = 18.6807(9) Å (at 140°C). In the reported crystal structures zolpidem molecules form stacks through - 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.

zolpidem; imidazopyridines; solid state; crystallography; X-ray powder diffractometry; structure solution by powder diffraction; Rietveld analysis; dehydration; stability

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