*3.3. Infrared and Raman Spectroscopy*

The IR spectrum of the ITR–TER cocrystal showed an intense band at 1705 cm<sup>−</sup>1, which was also present in the ITR and TER spectra, at 1698 cm<sup>−</sup><sup>1</sup> and 1675 cm<sup>−</sup>1, respectively (Figure 6a). Strong peaks in this range are normally caused by the stretching of C=O [31]. As this peak appears at a higher wavenumber in the cocrystal than in the parent compounds, this suggests that the new H-bond in the cocrystal might be weaker than the one in TER, as ITR does not form any intermolecular H-bonds. Another area of interest was the fingerprint region, between 1200 and 1300 cm<sup>−</sup>1. In the TER spectrum, a broad strong peak at 1281 cm<sup>−</sup>1, most likely from the –C–O–H vibration, was seen, while in ITR, a peak at 1271 cm<sup>−</sup><sup>1</sup> was assigned to aromatic C–N stretching [32,33]. In the cocrystal, a number of medium intensity bands were detected around this area.

Raman spectroscopy confirmed the presence of the new phase and the spectrum of the cocrystal (Figure 6b) was significantly different when compared to those of ITR and TER, which indicate interactions between the API and the coformer forming supramolecular interactions [34]. In the pure coformer, H-bonded dimers are formed by the –COOH groups, with the C=O moiety acting as the H-bond acceptor and the –OH moiety being the H-bond donor. In the cocrystal, the acid dimer arrangemen<sup>t</sup> is disrupted, which results in a shift of the peak assigned to the C=O stretching band to 1696 cm<sup>−</sup><sup>1</sup> in the cocrystal spectrum, while in the conformer, the band is located at 1633 cm<sup>−</sup>1. This effect was also observed by Shevchenko et al. [15], who investigated the formation of ITR cocrystals with aliphatic dicarboxylic acid of varying chain lengths, including succinic acid, malonic acid, and oxalic acid. In that work, the authors detected a peak shift of the C=O vibration in all produced cocrystals.

**Figure 6.** (**a**) Fourier-transform infrared spectroscopy (FT-IR) spectra of the ITR and TER starting material powders as well as the ITR–TER cocrystal prepared by ball milling (ITR–TER 2:1 BM); (**b**) Raman spectra of the ITR and TER starting material powders as well as the ITR–TER cocrystal prepared by ball milling (ITR–TER 2:1 BM). ν–stretching.
