Polymorphism can be seen in most active pharmaceutical ingredients (APIs), because of the various molecular structures and forms exhibited by compounds that can affect the efficacy, stability or bio-availability of the drug. These changes can develop during the formulation, packaging, storage and handling stages.
Manufacturers of pharmaceutical products must identify polymorphs rapidly and reliably in all stages of production, including development, manufacturing and quality control. This article looks at the advantages of the THz-Raman® systems against traditional methods in analyzing polymorphs in pharmaceuticals.
Rapid and reliable identification of polymorphs is critical in pharmaceutical manufacturing
Existing Techniques
Deducing the structural shifts in a compound can be realised in many ways, including; Raman spectroscopy, X-ray diffraction (XRD), and Terahertz (THz) spectroscopy. Raman spectroscopy is used to monitor any band shifts in the “fingerprint” region (200-1800 cm-1). However, these show small shifts for the functional groups, which are usually hard to detect during polymorphic or phase changes.
XRD techniques can achieve quantitative and conclusive analyses, but expensive equipment and destructive off-line testing is required to achieve this. THz spectroscopy can easily differentiate between structural shifts, but it does have a limited spectroscopic range, is costly, is moisture-sensitive and requires special sample preparation techniques.
Coherent Systems
The range of conventional Raman spectroscopy can be broadened using Coherent THz-Raman® systems. These systems extend Raman spectroscopy into the terahertz/low frequency region, where it is straightforward in differentiating the inter- and intra-molecular structures (Figure 1).
Figure 1. THz-Raman spectra for polymorphs of various APIs showing clear differentiable peaks.
Raw materials, synthetic pathways and contaminants can all be differentiated using THZ-Raman spectroscopy, which also opens it up as a useful tool for counterfeit detection and surety testing. The Raman intensity is also improved by Anti-Stokes signals and an improved SNR.
Coherent THz-Raman® systems provide a fast and unambiguous differentiation of polymorphs, while maintaining a complete “fingerprint region” in the Raman spectra for chemical identification.
Key Features
The key features and advantages of Ondax systems are as follows:
- Simultaneous structural and chemical analysis
- Quick and reliable identification of polymorphs, including isomers, conformers, hydrates, and co-crystals
- Useful for surety testing and counterfeit detection
- Non-destructive technique that does not need any sample preparation
- Compatible with traditional Raman spectrometers
- Compact, simple, and cost-effective
- Available in benchtop or microscope configurations at 532, 633, 785 and 830 nm
Single System Handles THz-Raman and Fingerprint Region Measurements
Many molecules undergo structural changes during formulation and processing methods, and under different environmental conditions. The figure below shows the spectra of two polymorphs of carbamazepine (Form 2 and Form 3) (Figure 2).
Figure 2. Two polymorphs of carbamazepine (Form 2 and Form 3).
The THz-Raman range (green background) shows clear and differentiating signals compared to the conventional fingerprint region (gold background), thus, improving the reliability and ease of which a polymorph can be identified.
Coherent's patented THz-Raman® Spectroscopy Systems broaden the scope of traditional Raman spectroscopy into the THz and lower frequency regimes. These systems can explore the same range of energy transitions as THz spectroscopy without reducing the ability to measure the fingerprint region. This enables a simultaneous analysis of molecular structure and chemical composition for advanced materials characterization.
All THz-Raman® systems are robust, compact, plug-and-play platforms, that provide speed, throughput and ease of use at an affordable price. They possess a wide selection of excitation wavelengths (from 488 to 1064 nm), a large number of sample interfaces and optional polarization control, enabling THz-Raman® solutions to be used for any application.
Figure 3. THz-Raman® systems showing benchtop, probe and microscope configurations.
This information has been sourced, reviewed and adapted from materials provided by Coherent.
For more information on this source, please visit Coherent.