Physicochemical characterization of tamoxifen citrate pseudopolymorphs, methanolate and ethanolate.
Two novel pseudopolymorphs, methanolate and ethanolate of tamoxifen [(Z)-2-[4-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine]citrate, were prepared in addition to forms A and B reported previously. Their crystalline forms were identified and characterized by powder and single crystal X-ray diffractometry, differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, scanning electron microscopy and diffuse reflectance infrared Fourier-transform spectroscopy, and their physicochemical stability was also evaluated. The results of single crystal X-ray analysis and thermogravimetric analysis of methanolate and ethanolate suggested that the stoichiometry of tamoxifen citrate : methanol and tamoxifen citrate : ethanol could be composed of a 1 : 1 molecular ratio for both solvates. The results of physicochemical stability evaluations at 75 and 97% RH at 40 and 60 degrees C indicated that the metastable form A was quite stable for at least 2 months even under severe storage conditions, whereas methanolate immediately transformed to a crystalline mixture of forms A and B, and subsequently changed to the stable form B.
Kojima
Takashi
T
Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Higashi-Nada, Kobe, Japan. tak_kojimajpn@yahoo.co.jp
Kato
Fumie
F
Teraoka
Reiko
R
Matsuda
Yoshihisa
Y
Kitagawa
Shuji
S
Tsuhako
Mitsutomo
M
D003460:Crystallization; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D013629:Tamoxifen / Q000737:chemistry*; D013696:Temperature
D013629:Tamoxifen