# Selected Applications of Terahertz Pulses in Medicine and Industry
## 3 Terahertz Spectroscopy in a Pharmaceuticals
\begin{table}
\begin{tabular}{c c c} \hline \hline
**Substance** & **Form** & **Reference** \\ \hline Anthranilic acid & I, II and III & [40] \\ Carbamazepine & I, II, and III & [39; 41; 42; 43; 44] \\ Diclofenac Acid & I, and II & [45] \\ Diflunisal & I, and III & [46] \\ Enalapril maleate & I, and II & [39] \\ Famotidine & A, and B & [47] \\ Flufenamic acid & I, and III & [48] \\ Furosemide & I, II, III, IV, and V & [49] \\ l-Glutamic Acid & \(\alpha\) and \(\beta\) & [50] \\ Indomethacin & \(\alpha\) and \(\gamma\) & [51] \\ Irbesartan & A, and B & [52] \\ Mebendazole & A, B, and C & [53] \\ Mefenamic acid & I, and II & [54] \\ Probucl & I, and II & [55] \\ Ranitidine HCl & I, and II & [38; 56] \\ Simvastatin & I, II, and III & [57] \\ Sulfathiazole & I, II, III, IV, and V & [58] \\ Theophylline & I, and II & [41; 59; 60] \\ Tolbutamide & I, II, and III & [61] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: List of published papers of substances with different polymorphs investigated with terahertz pulses. The understanding of the modes in the terahertz region has increased over the recent years, with work undertaken by the [PERSON] group at the University of Syracuse [45; 62] and more recently, the [PERSON] group at the University of Vermont [63]. These groups have shown that isolated molecule theory in the crystalline state is not valid. These groups have shown that is possible to assign transitions in solids in the terahertz region but the process requires an understanding of long-range forces within a substance. Drug substances are not only found in the crystalline state. It is becoming more common for pharmaceutical companies to manufacture amorphous materials, due to the poor water solubility of new chemical substances of interest. In the terahertz region, the absorption spectrum of amorphous materials is dominated by the vibrational density of states (VDOS) [64], yielding broad featureless absorption spectrum [65]. [PERSON] et al. [39] showed that the terahertz spectrum of amorphous indomethacin is broad and does not contain any well-defined features. [PERSON] et al. [43; 44] explored the relaxation processes in amorphous carbamazepine. In these papers an amorphous sample was heated while being monitored by a terahertz spectrometer. The authors reported a three stage dynamic process in which some of the material sublimed during heating process. They were able to estimate from the kinetics the amount of material in the gas phase during the process. This work was later extended to supercooled glass in substances such as paracetamol [66]. Figure 2: The terahertz spectra of different tablets containing ramididine hydrochloride (**a**) Zantac from Glaxo, (**b**) Norton (Ranbaxy Laboratories), (**c**) Eastern Pharmaceuticals Ltd. (Middlesex, UK), (**d**) Apotex Inc. (Toronto, ON, Canada), (**e**) Tilmed, and (**f**) Generics UK Limited. The ability to predict the stability of amorphous material in the pharmaceutical industry is important, as it can set a limit to the storage conditions or the lifetime of the product. Insights into the molecule mobility using terahertz pulses was provided by [PERSON] and [PERSON] [66], who used the mobility to predict the stability of amorphous materials [67; 68; 69] for a number of molecules, including paracetamol, indomethacin, flufenamic acid, and simvastatin. The Cambridge group suggest that the \(\beta\)-relaxation could be as a parameter that could predict the stability of amorphous drugs. The group from the University of Copenhagen were able to provide evidence for this using the orthogonal technique of X-ray powder diffraction [70].