Kevin P. Menard, PhD, business manager of thermal analysis at PerkinElmer (Shelton, CT)
Differential scanning calorimetry (DSC) and Raman spectroscopy are well-known techniques in pharmaceutical analysis. DSC determines
glass transitions, amorphous content, melting temperatures, and enthalpy and estimates the degree of crystallinity. In its
fast-scanning mode, DSC also suppresses kinetic changes (i.e., polymorphism and decompositions). This allows measurements
to be made before kinetic changes can occur, allowing one to determine the initial polymorphic form as well as measure melting
and heat capacity on materials before they decompose. Raman spectroscopy is able to detect changes in chemical composition
as well as positional and stereochemical changes in a sample; this allows it to identify specific polymorphic states. Raman
spectroscopy, however, has some difficulties in measuring temperature-dependent reactions such as dehydrations and polymorphic
rearrangements. These reactions are sensitive to the temperature applied, and care must be taken so that the energy added
by the Raman's laser does not affect the data by causing changes in the sample temperature (1). A combination of dual furnace
(i.g., power-compensated) DSC and a shuttered laser in an Eschelle Raman spectrometer were found to give minimal increases
in bulk sample temperatures (2).
As a hyphenated technique, however, DSC–Raman spectroscopy works well in detecting the changes in polymorphic materials as
a function of temperature (3). For example, running a sample of acetaminophen in heating showed a series of peaks corresponding
to changes in polymorphic forms, but the changes in the material corresponding to those thermal events are inferred (2). For
example, an endothermic peak in the DSC themogram can be a melt, a water loss, or a polymorphic change. Raman spectroscopy
allows one to confirm what the transition is; the chemical and structural changes detected from the Raman spectra clarify
the DSC data. Because the DSC can performed under a wide range of thermal conditions, including heating and cooling rates
from 0.1 to 750 ° C/min, the combined techinques can be used to characterize the materials' kinetic behavior under a wide
variety of conditions. For example, crystallization processes can be studied using DSC–Raman during cooling experiments. Other
work has been reported on hydrates and pseudo polymorphs as measuring the reaction of materials by tracking changes in assigned
bands in the Raman spectra and the energetic changes (4, 5).
DSC–Raman spectroscopy section references
1. R. Alexander et al., Proceedings of the North American Thermal Analysis Society (NATAS) Annual Conf. (Atlanta, 2008), pp. 131–136.
2. A Dennis, K. Menard, and R. Spragg, Proceedings of the Annual Technical Conf. of the Society of Plastic Engineers (Chicago, 2009), pp 647–653.
3. K. Menard et al., Am. Lab.
42 (1), 21–23 (2010).
4. N. Redman et al., Furey, , Proceedings of NATAS Annual Conf. (Albuquerque, NM, 2003), pp. 120–129;
5. A. Bigalow-Kern et al., J. ASTM,
2 (7), 42–61 (2005).