Preparation and characterization of a novel polymorph of indiplon, Form α.
A new polymorph α of indiplon was discovered, initially prepared by two methods, and further characterized by various means including single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), variable temperature powder X-ray diffraction (VT-PXRD), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), Fourier transform Raman (FT-Raman) spectroscopy and solubility determination. The crystal structure of Form α as analyzed by SCXRD differ from the three previously reported polymorphs, Form I, II, and III. In addition, PXRD and solubility measurements could clearly distinguish between Form α and Form I. Slight differences between the two forms were also detected by FT-Raman. No differences between Form α and I were observed by DSC, which was explained by VT-PXRD results showing a solid-solid phase change from Form α to Form I during the heating process. Solubility measurements at various temperatures showed that the two polymorphs were mutually monotropic and that Form I was the relatively thermodynamically stable crystal form.
Beijing Institute of Radiation Medicine, No. 27, Taiping Rd., Haidian District, Beijing 100850, PR China; Taizhou Central Hospital, No. 999, Donghai Rd., Jiaojiang District, Taizhou 318000, Zhejiang, PR China.
Lijun
L
Xu
Jing
J
Wang
Bingkun
B
Xiao
Jianyun
J
Yang
Yanru
Y
Liu
Rongqing
R
Huang
D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D033362:Powder Diffraction; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013816:Thermodynamics; D013818:Thermogravimetry; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry*
D013876:Thiophenes; D001569:Benzodiazepines; C469870:indiplon