Vibrational Spectroscopy in Pharmaceutical Development

Vibrational spectroscopy (VS) is the analysis of molecular properties based on vibrations at the molecular level and it is highly selective1. VS produces a spectral fingerprint of a material, such as an active pharmaceutical ingredient (API), so is well-suited to both identify and verify the API raw material and its presence in a final product. There are three related analytical techniques that use VS: Fourier-transform infrared (FTIR), near-infrared (NIR), and Raman. The objective of this technical brief is to compare these analytical modalities with an emphasis on the advantages that are inherent to Raman spectroscopy. Any advantage for a particular spectroscopy modality is rooted in the fundamentals of the measurement itself. A key difference between the Raman and either FTIR or NIR is that Raman is a scattering measurement and FTIR and NIR are absorption based. In absorption methods, the sample is exposed to a range of wavelengths of light and the amount of light absorbed by the sample is compared to a reference and a difference spectrum is produced. With scattering technologies, the sample is exposed to a single wavelength of light usually in the form of a laser and a range of wavelengths are monitored for light emitted. The light emitted is as a result of the interaction (Raman) of the material with that single wavelength light. The requirement of the FTIR/NIR technique to have a reference light path will limit the sampling and instrument configurations since the reference and sample light path lengths must remain similar and short. Absorption techniques are sensitive to the dipole vibrations in O-H, C-H, and N-H bonds whereas Raman is sensitive to polarizable vibrations like those present in C=C, C=N, C≡N, and aromatics. The dispersive technique is sensitive to the molecular backbone and analysis can be performed in Technical Brief 2011 Volume 7