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New Applications of Electron Diffraction in the Pharmaceutical Industry: Polymorph Determination by Using a Combination of Electron Diffraction and Synchrotron X-ray Powder Diffraction Techniques

Published online by Cambridge University Press:  14 June 2002

Z.G. Li
Affiliation:
Central Research & Development, Science & Engineering Laboratory, Experimental Station, DuPont Company, Wilmington, DE 19880-0228, USA
R.L. Harlow
Affiliation:
Central Research & Development, Science & Engineering Laboratory, Experimental Station, DuPont Company, Wilmington, DE 19880-0228, USA
C.M. Foris
Affiliation:
Central Research & Development, Science & Engineering Laboratory, Experimental Station, DuPont Company, Wilmington, DE 19880-0228, USA
H. Li
Affiliation:
Chemical Process R&D, DuPont Pharmaceuticals Company, Deepwater, NJ 08023-0999, USA
P. Ma
Affiliation:
Chemical Process R&D, DuPont Pharmaceuticals Company, Deepwater, NJ 08023-0999, USA
R.D. Vickery
Affiliation:
Pharmacy R&D, DuPont Pharmaceuticals Company, P.O. Box 80400, Wilmington, DE 19880-0400, USA
M.B. Maurin
Affiliation:
Pharmacy R&D, DuPont Pharmaceuticals Company, P.O. Box 80400, Wilmington, DE 19880-0400, USA
B.H. Toby
Affiliation:
Center for Neutron Research E151/235, National Institute of Standards & Technology, Gaitherburg, MD 20899, USA
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Abstract

Electron diffraction has been recently used in the pharmaceutical industry to study the polymorphism in crystalline drug substances. While conventional X-ray diffraction patterns could not be used to determine the cell parameters of two forms of the microcrystalline GP IIb/IIIa receptor antagonist roxifiban, a combination of electron single-crystal and synchrotron powder diffraction techniques were able to clearly distinguish the two polymorphs. The unit-cell parameters of the two polymorphs were ultimately determined using new software routines designed to take advantage of each technique's unique capabilities. The combined use of transmission electron microscopy (TEM) and synchrotron patterns appears to be a good general approach for characterizing complex (low-symmetry, large-unit-cell, micron-sized) polymorphic pharmaceutical compounds.

Type
MATERIALS APPLICATIONS
Copyright
2002 Microscopy Society of America

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