Fourier transform infrared (FT-IR) spectroscopy, Raman spectroscopy and thermal analysis are three valuable analytical tools for research and quality-control applications. Each method has its own strengths and weaknesses that make it ideal for some applications and not the best choice for others.
In general, Raman and FT-IR both look at the molecular structure of a material and thus are best suited for fingerprinting specific materials. Raman spectroscopy is the typically the fastest because it usually requires the least sample preparation time while FT-IR is less expensive and offers a wider range of sampling accessories. Thermal analysis tends to be complementary with Raman and FT-IR because it characterizes samples based on their bulk material properties.
Raman spectroscopy is based on the detection of scattered light. Upon collision with a molecule, a photon may lose some of its energy (Stokes radiation) or the photon may gain some energy (anti-Stokes radiation). When viewed with a spectrometer, both Stokes and anti-Stokes radiation are composed of lines that correspond to molecular vibrations of the substance under investigation.
Each compound has its own unique Raman spectrum that can be used as a fingerprint for identification. Raman spectra can be obtained from solids, liquids, gels, slurries, powders and polymer films. It is possible to obtain Raman spectra of gases, but this typically requires special equipment, such as long pathlength cells, because the concentration of molecules in gases is low.
Infrared and near-infrared (NIR) take advantage of the fact that each molecule’s functional groups absorb infrared radiation to generate a characteristic absorption or transmission spectrum that is rich in information and unique to that molecule. Spectra can be analyzed or searched against libraries of reference materials to identify unknown materials positively.
In the mid-IR range, bands are often strong, and samples usually require preparation processes that could involve diluting a powder or thinning a liquid or film in order to measure usable spectra. In the NIR range, absorptions are due to overtones, and combination bands of fundamental vibrations and are generally weaker and broader. While spectra are somewhat more difficult to interpret than in the IR range, a major advantage of FT-NIR spectrometers is that sample preparation is rarely required.
Thermal analysis comprises a number of different methods that look at properties of materials that change with temperature:
• Differential scanning calorimetry (DSC) measures the amount of energy absorbed or released by a sample as it is heated, cooled or held at a constant temperature.
• Thermogravimetric analysis (TGA) measures the change in weight of a sample as it is heated, cooled or held at a constant temperature.
• Thermogravimetric/differential thermal analysis (TG/DTA) combines the two previous techniques to measure both heat properties and weight changes in a sample simultaneously.
• Dynamic mechanical analysis (DMA) measures the changes in mechanical behavior, such as modulus and dampening, as a function of temperature, time, frequency, stress or a combination of these parameters.
• Thermomechanical analysis (TMA) determines dimensional changes in materials as a function of temperature or time.
Figure 2. Raman analysis of pharmaceutical powder through a plastic storage bag.
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Raman vs. FT-IR
Both Raman and FT-IR generally provide similar molecular identification results, so they tend to be competitive. A key advantage of Raman spectrometry is that it requires little or no sample preparation. In fact, samples can even be analyzed without removing them from their packaging materials, such as a glass bottle or plastic bag, making the technique particularly useful in various forensic and pharmaceutical applications.
Raman instruments have historically been much more expensive than FT-IR instruments because they require high-stability laser sources. Over the past 10 years, however, technology advancements have improved the sensitivity of Raman detectors while costs have dropped substantially.
In many applications, the extra cost of Raman spectroscopy can easily be justified in productivity savings. The analysis can usually be performed with a probe connected to a long fiber cable that leads back to the instrument, which may be located in a different part of the facility.
As such, instead of taking the sample back to the lab, the analysis can be performed in the shipping department or on the production floor by an operator who is not skilled in using the instrument. The actual analysis time for Raman and FT-IR spectroscopy are usually comparable.
FT-IR instruments are considerably less expensive than Raman spectrometers, but the sample normally has to be made less than 100 microns in thickness. In the last decade or so, a range of sampling accessories has simplified sample preparation. Reflection techniques, for example, eliminate the need to make the sample thin.
FT-NIR spectrometers provide an interesting alternative to Raman and FT-IR. FT-NIR absorbances are not as strong, which in most cases eliminates the need for sample preparation, increasing analysis speed and enabling non-destructive testing. For example, in many cases, a fiber optic NIR probe can simply be inserted into a bin of raw materials or blend and the chemical, and often the physical properties of the material can be analyzed. An LCD display, located on the probe itself, shows the operator the “go” or “no-go” result. Because NIR spectra can be more overlapped, NIR methods often require more careful development, particularly with regard to data processing techniques. After validation, FT-NIR provides very accurate analysis results.
Thermal analysis applications
As a general rule, FT-IR, FT-NIR and Raman overlap to a considerable degree, although there are some applications where they are complementary. On the other hand, thermal analysis is a bulk method that is nearly always complementary to all three methods.
• FT-IR can tell the impurity in a biological pharmaceutical while DSC can indicate that the pharmaceutical is 97 percent pure.
• FT-IR can tell that the sample is polyethylene while DSC tells whether it is linear low density or ultra molecular weight polyethylene based on the melting points.
• FT-IR and Raman can determine the chemical groups present in protein-based drugs while DSC can measure the glass transition prime (Tg') of its solution as an indicator of the collapse temperature.
• Raman or IR can give the structure of a pharmaceutical while DMA can determine its glass transition temperature, which affects its storage temperature.
• IR can give the information about the chemical composition of a drug while DSC and Raman can look at its polymorphic forms, which affect its biological activity.
• DMA, on the other hand, is useful for testing material properties, such as hydrogel delivery systems’ use for smoking cessation and birth control drugs, or the properties of materials used in biomedical devices, stents and pacemakers.
FT-IR, Raman and thermal analysis are three of the most powerful analytical tools used in pharmaceutical research, fine chemical, bulk chemical, polymers, petroleum, food and beverage, and paper and packaging industries, as well as forensic and educational teaching and research applications. Thus, understanding the pluses and minuses of each of these tools will help increase productivity and robustness of numerous analysis tasks.
For more information, contact Nicola Scott with PerkinElmer Inc., at Nicola.Scott@perkinelmer.com or visit www.perkinelmer.com.