Detection of low levels of amorphous materials using H/D exchange, FT-Raman and FT-Infrared spectroscopy.

C. S. Stapleton,1 F. W. Harun,1 P. T.Whiteside,2 A. Parker,2 S. Y. Luk,2 J. J. Titman1 and M. W. George.1

1The University of Nottingham, University Park,Nottingham, NG7 2RD, UK. 2Molecular Profiles Ltd., 8 Orchard Place, Nottingham Business Park, Nottingham, NG8 6PX, UK.


In drug development, emphasis is placed on the importance of achieving reproducibility in terms of the biological, chemical and physical properties of a material. The presence of the amorphous phase within the material can have a significant effect on both the chemical and physical properties of the drug and excipient even if it is present at low levels (<5%). Within the industry many techniques are employed to try and quantify low levels of amorphous materials including DSC, DVS, PXRD, FTIR, FT-Raman and ss-NMR. There are limitations in each of these techniques in terms of quantification and/or sensitivity. Here we demonstrate the use of H/D exchange with FT-Raman and FTIR spectroscopy to quantify low levels of amorphous materials of both cimetidine and lactose. Notably we have studied mixtures of amorphous and crystalline material exploiting the fact that hydroxyl and amine hydrogen atoms are susceptible to deuteration in the amorphous phase, while in the crystalline phase they are not.

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