Low frequency Raman spectroscopy in pharma inspection

14 May, 2020

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New editorial editorial in Wiley’s Physics Best April 2020.

Low frequency Raman spectroscopy: How narrow-line diode lasers facilitate pharmaceutical inspection

Read the full editorial here

Recently there is also a lot of interest in accessing the low-frequency Raman spectroscopy region (<10 cm-1 to 200 cm-1). Raman shifts in this frequency range give access to lattice vibrations of molecular crystals and have the potential to more directly probe intermolecular interactions in solid materials. The low-frequency Raman region probes the same low-energy vibrational and rotational modes of molecular structures as terahertz spectroscopy (300 GHz – 6 THz). The THz region of Raman spectra contain important structural information about the molecules or crystal lattices under investigation. In the pharmaceutical industry, for instance, this structural information can help to determine the crystallinity, and therefore solubility, of pharmaceuticals. Specifically, low-frequency Raman spectroscopy provides an avenue to probe polymorphic structures of pharmaceutical systems before and after tableting, as well as drug identification and quantitation for crystalline materials, both of which are critical quality attributes in pharmaceutics.

Being able to determine the structural form of the Active Pharmaceutical Ingredients (API) is a primary objective in the pharmaceutical industry during drug development, manufacturing and quality control. APIs exhibit polymorphism, which is characterized as having identical chemical compositions but different solid-state structures that may affect the bioavailability and therapeutic index, which could lead to compromised efficiency of any final drug product [2-3]. Probing the low frequency Raman region has several advantages over existing techniques such as ease of collecting data (compared with tradition methods such as X-ray powder diffraction and differential scanning calorimetry), collecting spectrum rich in structural information as well as being able to discriminate crystalline forms.

Narrow-line diode lasers for low frequency Raman

Laser sources suitable for Raman spectroscopy at 785 nm can be fabricated from AlGaAs-based semiconductor devices. Depending on the emitter size and geometry they can be designed to emit single-transversal mode beams (lower power) or multi-transversal mode beams (higher power). Semiconductor lasers have a broad gain spectrum and typically have bandwidths of over 1 nm and with long spectral tails stretching several 10s of nm from the main peak. They can be made to emit spectrally single-mode radiation by introducing distributed wavelength selective gratings (DBR/DFB) into the structure. DBR/DFB lasers at around 780 nm are available at up to a few 10s of mW output power. As an alternative for higher power levels, it is possible to turn the broad-band emission from a semiconductor laser into narrow-band by building an external cavity with a separate wavelength-selective cavity element. In this way the stimulated emission from the laser will be frequency-locked to the spectral distribution of the feed-back from the external cavity element. A conventional way of constructing such frequency-locked semiconductor laser is to build an external cavity using a Volume Bragg Grating element (VBG).

 

Authors: Dr Peter Jänes & Dr Håkan Karlsson, Cobolt, a part of HÜBNER Photonics.

Read the full editorial here

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