▶ Raman and polymorphic analysis
Basic Information

Raman spectroscopy has only recently arisen as one of the commonly used molecular motion probing techniques. The invention of Raman spectroscopy goes back to 1928 when the Indian physicist C.V. Raman first found that the wavelength of a small fraction of the radiation scattered by certain molecules differs from that of the incident beam. This discovery led Raman to be awarded the Nobel Prize in Physics in 1931.


Chandrasekhara Venkata RAMAN, 1928

The energy levels explored by Raman spectroscopy are the same as those in IR spectroscopy. However, the two techniques are based on different molecule vibrations. Molecules must have a dipole moment change to be IR activate, while their polarity must change (i.e. their induced dipole moment) to be of Raman active. Therefore, information obtained from Raman and IR are complementary.  

While not necessarily the best choice for every application in the pharmaceutical industry, a critical appraisal reveals that in certain circumstances Raman spectroscopy possesses a number of compelling practical advantages over IR, for instance simple (or no) sample preparation, low scattering of water, and fewer and more distinctive peaks. This has been demonstrated to good effect, for example in the area of pharmaceutical polymorphs analysis.

Building on decades of experiences developing analytical methods especially combining Raman technology with multivariate analysis, we promise to deliver the reliable analytical solutions for your specific formulation and process.

As shown by the figure below, spectral differences between four CBZ polymorphs can be clearly observed.

Raman spectra of CBZ polymorphs (Arrows show area of spectral differences between the samples).

The two batches of form I, 1st and 2nd batch, were of different morphology. Such morphology difference however had almost no influence on its Raman scattering.

The same samples were also measured by XRPD (as shown below). The relative height of some peaks however was different between the two batches of form I.

                    X-ray diffractograms of CBZ polymorphs.

SEM demonstrated that form I (1st batch) consisted of needle like crystals, while form I (2nd batch) was of prism like crystals. Preferred orientation was likely to be induced when the needle like crystals form I (1st batch) were packed in the XRPD sample holder.

SEM micrographs of CBZ polymorphs: A) form I (1st batch); B) form I (2nd batch); C) form II; D) form III (horizontal scale bars: 1.00 mm).

Compared to XRPD, Raman demonstrated a more robust nature in quantitative analysis. Problems such as different morphology, particle size, and spatial distribution of the two solid state forms of the drug might have minimal influence on Raman scattering. 


Further reading:

Tian F, Zeitler JA, Strachan CJ, Savllle D, Gordon KC, Rades T Journal of Pharmaceutical and Biomedical Analysis 2006, 40:271-280

Tian F, Zhang F, Sandler N, Gordon KC, McGoverin CM, Strachan CJ, Saville DJ, Rades T European Journal of Pharmaceutics and Biopharmaceutics 2007, 66: 466 – 474

API and excipients

APIs often have much stronger Raman scattering than pharmaceutical excipients. Raman can thus be utilized for a rapid identification and quantification of API in the pharmaceutical formulation.  

Raman spectra of cellulose, carbamazepine and maize starch measured under identical conditions and on the same intensity scale (figure below).

Raman shift / cm-1 

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