Terahertz radiation has excellent potential in the advancement of process understanding but is, as yet, largely unexplored. Recent developments in semiconductor physics have made it possible to provide light at terahertz frequencies (a frequency of 1 THz equals a wavelength of 0.3 mm) in a relatively simple way. Light located in this range of the electromagnetic spectrum was very difficult to generate previously. It has unique properties in that it easily penetrates through most plastics and polymeric materials used for pharmaceutical tablets and, at the same time, it reveals a wealth of information about the medium and long range interaction of small organic molecular crystals, the typical active ingredients of most modern medicines. Terahertz time-domain spectroscopy (THz-TDS) is an ideal probe for the characterisation of pharmaceutical solids [1]. It is non-destructive and interacts with vibrational modes that extend across large domains of the lattice in organic molecular crystals. The ability to probe the lattice dynamics which represent interactions between molecules in their crystal structure makes terahertz spectroscopy a very powerful tool for the analysis of complex solid-state materials properties.

In terahertz pulsed imaging (TPI) terahertz light can be used to scan through a tablet and exhibit its internal structure [2]. Most of the excipients that make up the bulk of a tablet are transparent to terahertz light, whereas the drug and interfaces from different coating layers or substructures within the tablet lead to a contrast in the images. When ultrashort pulses of coherent terahertz radiation are directed onto the surface of a coated tablet, the thickness and density of all coating layers can be determined non-destructively. By mapping over the whole surface of the tablet the statistical distribution of the coating and its quality can be quantified. Even though the spatial resolution of terahertz images in the x and y direction is limited by diffraction to about 200 μm, the axial resolution, a function of the pulse duration, is better than 30 μm. The major challenges that limit the rapid development of novel applications of terahertz radiation in process research are its strong absorption by water, the need for more powerful sources, the lack of array detectors and waveguiding technology, and the poor understanding of the fundamental physics behind the contrast mechanisms in terahertz imaging.

A very novel source of terahertz radiation is a quantum cascade laser (QCL), which can provide high power terahertz radiation at a single frequency [3]. In principle, a QCL is a semiconductor laser using intersubband transitions. It measures only a few millimetres and has the potential to be built very cheaply. Even though the development of THz-QCLs is in its early phase and the present designs require to be operated at temperatures below 160 K, these lasers have a huge potential for imaging applications [4].

[1] J.A. Zeitler et al., J. Pharm. Pharmacol. 59, 209 (2007).
[2] J.A. Zeitler et al., J. Pharm. Sci. 96, 330 (2007).
[3] R. Kohler et al., Nature 417, 156 (2002).
[4] K. L. Nguyen, M. L. Johns, L. F. Gladden, et al., Optics Express 14, 2123 (2006).

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