TG_IR of the complex decomposition of a pharmaceutical studied by TG-IR. The left hand figure show the weight loss and derivative of the drug on heating in a TGA. The right hand figure shows the the map of the offgas as analyzed in the FTIR, plotting time, wavenumber, and absorbance. Data taken from work by Dr. M. Garavaglia of PerkinElmer Italy [6]

The advantage of MS and GCMS over FTIR for these applications is much lower detection limits. This can be a great advantage in situations where the weight loss consists of multiple solvents as shown in Figure 3 and the individual components are below the limit of detection by IR. Because of this sensitivity we can also look at leachates and contaminates in the sample as well as degradation products from improper storage.


An overlay of the TGA curve with the mass ions for the fragments for ethanol/methanol, acetone and water shows how TGA-MS allows the determination of the components. Data is taken from work described in the PerkinElmer Application Note on TG-MS by T. Mann et al.

Spectral DSC: Getting the Best of Both Worlds.

As discussed above, DSC is a powerful technique for studying transitions in materials from polymers to foods to pharmaceuticals, but the information is often incomplete in that structural or chemical information is inferred from the thermogram. For example, DSC allows users to see the transitions between crystalline forms in a drug or a food, but the forms must be determined by another method. Similarly, DSC can provide the energy and temperature of a change that occurs by either heating or photo-initiation, but other information, such as the specific chemistry of a particular part of the molecule must be inferred. Contra wise in Raman spectroscopy, it is easy to track a band associated with a specific bond, such as the sulfur bond in an ring system, but changes in the amorphous material from rigid to mobile, the glass transition, can be difficult to see. A simultaneous technique like DSC-NIR (near-infrared) or DSC-Raman solves these problems. Raman is often preferred for this coupling as it contains greater structural information [7] (Figure 4).


Raman and NIR spectra for acetaminophen are compared showing the greater detail in the Raman Spectra. Data collected by Dr. R. Spragg and J. Sellors of PerkinElmer ASLS

Combining the two techniques allows us to apply the precise temperature control of the DSC with the ability of Raman to detect the different polymorphic structures, and obtain precise characterization of the material. As an example, consider the common painkiller, acetaminophen. Raman spectroscopy has identified the three solid-state forms of this material found under these experimental conditions (note: there is also a fourth form not seen here). Combining this technique with DSC allows us to measure precisely the temperatures at which they occur. The thermogram shows two exothermic events believed to correspond to polymorphic changes in the material as well as the endothermic melt. When DSC-Raman is performed, the Raman spectra show the conversion to form II at ~90 ºC and then to form III at ~151 ºC before melting. This greatly simplifies our understanding of the thermal behavior of the material and is much more conclusive than attempting to draw this information out of either conventional and/or modulated temperature DSC or Raman spectroscopy alone.

Also of interest in combined DSC and Raman spectroscopy is the study of hydrates [8] and pseudo-polymorphs. These materials show changes caused by the loss of water or some other solvate from the molecule that appears as an endothermic transition. While Raman spectroscopy with a hot stage might determine the changes in the material accurately, without understanding the thermal data and the energy of transition, it is possible for a water loss to be seen as a polymorphic transition. In DSC, this can be detected as an endothermic event and hence become suspect.

Conclusions

Recent advances in analytical techniques allow pharmaceutical manufacturers methods to have greater control and understanding of their processes. More information can now be obtained in less time and often at lower cost.

About the Author

Kevin P. Menard, PhD, MBA, is Business Manager in Thermal Analysis at PerkinElmer.

References

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