Pharamaceutical AnalysisThe Challenge:

Many active pharmaceutical ingredients (APIs) exhibit polymorphism, where different forms or molecular structures of a compound can dramatically affect the efficacy, stability and bio-availability of the drug. These structural changes may occur during various stages of formulation, storage, packaging and handling. Consequently, rapid and reliable identification of polymorphs during the development, manufacturing, and quality assurance process is critical in pharmaceutical manufacturing.

Traditional Solutions:

Observing structural shifts of a compound can be accomplished several ways. Raman spectroscopy is used to observe small band shifts in the “fingerprint” region (200-1800 cm-1), however these reflect subtle shifts in functional groups and are difficult to detect for some polymorphs. X-ray diffraction (XRD) techniques yield extremely quantitative and conclusive analysis, but require expensive equipment and destructive off-line testing. Terahertz (THz) spectroscopy can easily differentiate structural shifts, as these signals correspond to large scale motions in the molecular and inter-molecular structure, however THz spectroscopy has limited spectroscopic range, is expensive, and can require special sample preparation.

The Ondax Solution: One Sample, One System, One Answer

API Polymorphs

THz-Raman Spectra of common API polymorphs. Data courtesy Dr. Tatsuo Koide, National Institute of Health Sciences, Division of Drugs, Tokyo, Japan

Ondax THz-Raman® systems extend the range of traditional Raman spectroscopy to the terahertz/low frequency regime, where differentiation of inter- and intra-molecular structures can be clearly seen. THz-Raman spectra can also be used to differentiate raw materials, synthetic pathways, and contaminants, useful for counterfeit detection and surety testing. Anti-Stokes signals add to Raman intensity and improve SNR. Combining both composition and structural analysis eliminates the need for multiple samples and instruments, lowering capital, training and maintenance costs..


  • Simultaneous chemical AND structural analysis
  • Fast, reliable polymorph identification, including hydrates, isomers, conformers and co-crystals
  • Useful for counterfeit detection/surety testing
  • Non-destructive and requires no sample preparation
  • Compatible with existing Raman spectrometers
  • Simple, compact, cost-effective
  • Available in benchtop or microscope configurations at 532, 633, 785, 830 and 976nm
Carbamazepine (CBZ)

Low Frequency Raman Spectrum of Carbamazepine

Low Frequency Raman Spectrum of Carbamazepine.The strong, distinctive peaks in the low-frequency/THz-Raman region (green background) are typically higher than the traditional fingerprint range, adding signal, improving sensitivity and reliability. Peak symmetry about the excitation line also enables auto-calibration and enhanced system and data reliability.

HMTD Low Frequency THz-Raman Spectra

THz-Raman CBZ


Low frequency/THz-Raman Spectra of CBZ

Low Frequency/THz-Raman spectra of CBZ Polymorphs Forms 2 and 3, plus Hydrate


Caffeine Cocrystals

Caffeine Cocrystals

THz-Raman spectra of caffeine and 2-benzoic acid, showing the shift in spectra when cocrystals are formed


Common APIs

Low frequency THz-Raman spectra of common APIs

Complete Raman spectra of common APIs. Note stronger intensity in THz-Raman region