Many industries use Raman spectroscopy to identify the composition of a gas or sample. This technique is now being extensively used to ensure the quality assurance of the development processes.
However, most of these measurements are performed in a point sampling manner, which may lead to incorrect measurement. One way to overcome this problem is to conduct transmission Raman measurement. This method allows exact measurement of the sample under target.
As one of the largest industries in the world, pharmaceuticals are worth approximately US$800 billion and are anticipated to grow at a rate of 5% per annum. They are also the highest value-added industry in the UK, and as such significant investment is made in pharmaceutical research.
However, a major problem of this industry is counterfeit products, which according to Sanofi, take 10% of the market share. As a result, advanced detection techniques are required to not only ensure consumer safety, but also to safeguard the investment made by this industry.
Transmission Raman
Transmission Raman can be used for those applications where counterfeit detection and quality assurance are of utmost importance. The present market for Raman measurements is earmarked to be £200 million, with the pharmaceutical market estimated to be approximately £60 million.
Indeed, the market for transmission Raman measurements can grow exponentially if better and more flexible detection techniques are available.
Figure 1 shows a standard illumination setup for a transmission Raman measurement. The light that comes out from the sample has a weak signal and as such each photon is very important.
When the laser enters the sample, Raman photons are activated, but when the light exits the sample, the photons disperse from a large 2mm-diameter area and exhibit a considerable target etendue. In order to match this etendue, the spectrometer is used so that light does not get lost.
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Figure 1. Typical transmission Raman arrangement
Image Credit: IS-Instruments
IS-Instruments has designed the HES series of spectrometers that provides 100X greater etendue when compared to conventional Czerny Turner instruments. The HES series has a number of features. For instance, the spectrometers do not have slit, can be combined to a 0.22NA fibre of 1-1.5mm diameter without any loss of light, and simultaneously achieve superior resolution. These aspects make the HES range of spectrometers suitable for transmission Raman measurements and possibly streamline a transmission Raman quality control system with minimum cost.
Experimental Framework
Spectrometer
A bespoke IR model of the HES 2000 spectrometer was used for the experiments. Here, operation performed at the IR wavelengths has a tendency to reduce fluorescent signals emitted by the sample, and when measurements are performed through a 785nm laser detector noise would be higher.
Due to its spectral width, the laser thus employed for the experiment had to be passed via two clean up filters. Therefore, the sample intercepted approximately 70mW of light. For the study, the spectrometer was combined to a 2mm-diameter fibre having a 0.22 Na. Table 1 shows the specifications of the illuminating laser and the spectrometer.
Table 1. Raman spectrometer specifications
| Parameter |
Specifications |
Notes |
| Illuminating wavelength |
1064 nm |
|
| Laser power at Tablet |
70 mW |
Laser provided 100 mW, but had to be passed through two clean up filters. |
| Spectral range |
30 - 1850 cm-1 |
|
| Spectral resolution |
< 8 cm-1 |
|
| Fibre input aperture |
Up to 3 mm diameter |
For experiments a 2 mm core fibre was used with a 0.22 Na (a 50 % insertion loss was observed at the collection fibre) |
| Detector type |
AndorIDus |
Cooled to – 70 C |
| Number of pixels |
512 |
|
| Pitch |
25 × 500 µm |
|
Sample
Figure 2 shows an image of the ibuprofen sample used for the experiment. In order to remove the sugar coating from the sample, one side of its surface was grounded. Following this, the Raman response was measured in a backscatter configuration from both surfaces of the sample. Measurement in a transmission Raman setup was also carried out.
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Figure 2. Sample Ibuprofen tablet
Image Credit: IS-Instruments
Results and Discussion
Figure 3 shows the Raman spectra obtained from the sample in a transmission configuration. With a 10 second-integration time, the observation was made to render a clear response; however, the spectrum was clear within a matter of seconds. The wide complex feature in the spectrum ranged from 230 to 600cm-1 and from 600 to 1830cm-1 where a standard Ibuprofen profile was determined.
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Figure 3. Transmission Raman spectrum of Ibuprofen (integration time 10 seconds)
Image Credit: IS-Instruments
Figure 4 shows the backscatter Raman response obtained from the white side of the tablet, with an integration time of 3s. A clear difference can be observed between both measurements, specifically the wide feature from 230 to 600cm-1 was significantly reduced. This implies that this characteristic is the response of the coated surface.
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Figure 4. Backscatter Raman measurement white side of the sample intercepted by the laser.
Image Credit: IS-Instruments
After rotating the tablet, the response from the pink surface was determined, as shown in Figure 5. The spectral response thus obtained was found to be considerably different from the two observations made before. A strong broadband feature between 230 and 1000cm-1 was observed, which is a standard fluorescent feature produced by sugar coating of the tablet. If this tablet was filed or determined in a factory, the following would be the response.
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Figure 5. Backscatter Raman measurement pink side of the sample intercepted by the laser.
Image Credit: IS-Instruments
All three Raman measurements of the tablet were made on the same plot, as shown in Figure 6. The transmission Raman renders a clear response from the tablet, thus demonstrating the effectiveness of this method.
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Figure 6. Raman spectra of Ibuprofen in all configurations, Black line = Transmission, Red line = Pink side backscatter, Blue Line = white side backscatter.
Image Credit: IS-Instruments
Conclusion
This article shows the ability of the IR HES 2000 spectrometer in performing a true transmission Raman measurement of the sample under target. In this case, an Ibuprofen tablet was determined from both sides and the Raman response clearly showed a bias to the sample’s top surface. The coated surface displayed a fluorescent-type response that possibly hides the Raman signal.
When the tablet was observed in a transmission configuration, the response from the entire tablet reduces the dominance of the surface which is coated. Thanks to the etenude feature rendered by the HES 2000 spectrometer, the measurement is performed with a short integration time.
This information has been sourced, reviewed and adapted from materials provided by IS-Instruments Ltd.
For more information on this source, please visit IS-Instruments Ltd.