Polymorphism in drugs investigated by low wavenumber Raman scattering

Raman scattering is a powerful method to investigate the polymorphism in drugs due to its remarkable sensitivity to the crystalline structure of molecular compounds. The sensitivity of the technique is strongly enhanced when considering the low wavenumber Raman active vibrational modes, since molecular skeleton deformations, librations and translations usually lay below 200 cm−1 and are directly related to the polymorphism phenomenon. In this work, the potential of the low energy Raman spectrum in the investigation of polymorphism of drugs is discussed. Several examples are presented showing the use of this spectral range in the understanding of the mechanism involved in the polymorphic behavior of active pharmaceutical ingredients. The results show that low wavenumber Raman spectra can be used for rapidly and accurately identifying the polymorphic forms of an active ingredient. Additional valuable information is obtained when combining spectroscopic measurements with ab initio calculations, X-ray diffraction measurements and thermal analysis.