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Measurement of pharmaceutical active ingredients and excipients

1st April 2013


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Nick Barnett outlines developments in Raman spectroscopy.

Low Resolution Raman Spectroscopy (LRRS) is a very useful technique for non-destructive chemical analysis and has gained increased attention and acceptance in the analytical laboratory as an affordable, robust and convenient alternative to cumbersome wet chemical analysis or expensive FT-Raman and FT-IR spectrometers.

Unlike high-resolution Raman spectrometers that are often capable of resolving peaks of less than three or four wave numbers apart, the new miniaturized systems relinquish resolution in favour of emphasizing basic identifying spectral features, or fingerprints, that are often distinct and clearly separated. Recent advances allow some of the high-end LRRS systems to compete around the 4cm-1 resolution.

The introduction of the silicon-charged coupled device (CCD) detector was the first technological development to enable LRRS. The CCD sensor has replaced the more light-sensitive single-element detectors such as the photomultiplier tube and avalanche photodiode. Integrated into a well-designed optical bench, the CCD can allow for resolution as fine as 4cm-1. A back-thinned CCD detector, which is more sensitive than a standard CCD, has been integrated into Raman spectrometers allowing for 6cm-1 resolution, increased quantum efficiency and high signal to noise. Advances in these devices have improved wavelength stability and increased S:N ratio, both crucial factors in building libraries and performing unambiguous spectral identification of raw materials.

Ocean Optics offer different Raman Spectroscopy options for their customers. Our approach to this market is based on OOI sales philosophy of applications customisation sales and service. Some of the available Raman analysis options include Ocean Optics spectrometer-based systems (modular) using the QE65000 as the detector platform with accessories (lasers and probes) provided by partner companies. Turnkey Raman Systems which uses OOI spectrometers as their detection devices provide the next option. These ready to use systems offer different resolution, sensitivity and laser wavelength options, including a low-resolution hand held device and desktop units. The main advantage of these instruments is their software, which better focuses on applications and includes the capability of creating and maintaining a spectral library.

Raman spectroscopy offers a number of benefits for testing and characterisation. Like regular IR spectroscopy, it is rapid and non-destructive. Unlike IR spectroscopy, which falls spectrally within the water window, Raman spectroscopy can be used to capture data on aqueous samples or samples with high moisture content.

So, how to select between a Raman system with a 785nm laser and one with a 532nm laser? The 785nm version is designed to minimize the fluorescence signal, making it useful for chemical identification and fingerprinting. What's more, the 785nm version generates well defined peaks for use in chemometric analysis and can provide semi-quantitative data. For applications where C-OH structural information is important, the 532 nm version is your best option. Such measurements are typical of biological and pharmaceutical sample analysis, where researchers study characteristics of active ingredients, binders, fillers, lubricants and excipients.

Raman techniques can be used to acquire data through vial walls, pill pack windows and bags - packaging forms that are frequently used in the biomedical and pharmaceutical industries. A typical application for the pharmaceutical market is the capability of discerning pharmaceutical raw materials such as active ingredients, binders, fillers, lubricants and other excipients commonly used by this industry. Today, portable Raman instruments allow authorities to detect counterfeited pharmaceuticals and contaminated raw materials. To illustrate the capabilities of Raman spectroscopy Ocean Optics has analysed the following pharmaceutical active ingredients (Paracetamol and Carbamazepine) as well as two commonly used excipients (alpha and beta Lactose).

The samples studied consisted of simple organic compounds including excipients and active pharmaceutical ingredients. They were contained in standard, clear borosilicate scintillation vials with no additional preparation applied. Most samples were purchased or obtained from a major pharmaceutical company.

The samples were analysed using an Ocean Optics QE65000 Raman-configured spectrometer incorporating a back-thinned, cooled detector array. For the light source we used a 785nm laser specifically developed for Raman spectroscopy with 500mW output and a narrow spectral line width of only 0.2nm. Light was delivered to and collected from the sample using a fibre optic probe specifically designed to work at the laser wavelength with appropriate filtering to remove the Rayleigh laser line. In order to take the measurements the tip of the probe was placed at the bottom of the glass vials containing the samples. The samples were measured using an integration time of 8 seconds and averaging three readings.

The system picture illustrates the overall modular set-up, including the QE65000 spectrometer (black), the laser (white) and the fibre optic Raman probe.

Conlusion

The spectra obtained in this study show the typical Raman features for these active and excipient substances. This demonstrates that such a modular approach to Raman instrumentation can be used to discern the main features of these pharmaceutical samples and differentiate the different raw materials based on their spectral fingerprint. Furthermore, with proper method development and chemometric techniques, this approach may help obtain semi-quantitative data of the active ingredient content in a pharmaceutical mixture.

Enter √ www.scientistlive.com/eurolab

Nick Barnett - UK Country Manager, Ocean Optics BV, Duiven, The Netherlands. www.oceanoptics.eu

References:

1. R H Clarke, S Londhe, and M E Womble, "Low-resolution Raman Spectroscopy as an Analytical Tool for Organic Liquids", Department of Chemistry and Photonics Center, Boston University, Boston

2. R H Clarke, S Londhe, W R Premasiri and M E Womble, "Low Resolution Raman Spectroscopy Instrumentation and Applications for Chemical Analysis", Clarke Journal of Raman Spectroscopy, 1999, Vol 30: pp. 827-832.

3. J Macho, "Practical Mobile Raman Spectroscopy", Raman Technology for Today's Spectroscopists, Spectroscopy, June 2007

4. M Schmitt and J Popp, "Raman Spectroscopy at the Beginning of the 21st Century", J Raman Spectroscopy, 2006 Vol 37: pp. 20-28.


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