THz Raman for Polymorphic form and crystal / amorphous measurements

Low wavenumber ("THz") Raman provides strong signals from the crystal lattice. These Raman bands are nearly an order of magnitude more intense than the rest of the Raman spectrum, characteristic of the polymorphic form and their presence confirms crystallinity whilst their absence confirms that the sample is amorphous.

Measurement of the strength of the bands can be used to calculate the crystalline/amorphous ratio.

In situ polymorphic transformation

Measuring Raman lattice modes below 200cm-1 to monitor phase transitions has been demonstrated as an excellent laboratory tool. The transformation of theophylline between forms has also been studied with other techniques. New notch filter technology now permits Raman measurements to be made below 200cm-1 and this shows the utility of using lattice modes to monitor polymorphic form rapidly in real time by following the transformation of anhydrous theophylline (Form II) to a monohydrate (Form M) as an aqueous slurry.The Ondax TR Probe was used to monitor the transformation and the THz Raman spectrum, time series spectra of the transformation and transformation profile are shown on the right.

•Raman spectroscopy is ideally suited to monitoring many heterogeneous systems such as slurries.

•Raman spectroscopy in the low wavenumber region below 200cm-1 provides useful information on polymorphic form.

•The high intensity of the lattice modes in this region improves sensitivity when compared with molecular modes (7:1 in this case)

•There is no Raman spectral interference from solvents and solutes in this region.

•Sharp peaks from crystalline solids are readily distinguished from broad solvent boson peaks.

Degree of Crystallinity

Because the THz Raman spectra are the vibrations of the crystal lattice and amorphous materials will show no Raman bands, the intensity of the bands is proportional to the degree of crystallinity. Figure one shows the THz Raman spectra of 1-20% crystalline material, blended with the same material in it's amorphous form. Figure 2 shows the Raman signal (peak intensity) plotted against %w/w crystalline material and illustrates that THz Raman is an excellent tool for determining the crystalline/amorphous ratio.

Ondax THz Raman probe