3.3.2. FTIR Measurement Data

In the crystal arrangement, FTIR has commonly used to detect the hydrogen bonding formation [37–45]. Figure 3a reveals infrared spectra of NDH, LP, physical mixture 1:1 (PM), and NDP crystals from ethanol, methanol, and acetone, respectively. FTIR spectra of NDH indicated the water –OH stretching band at 3200–3500 cm<sup>−</sup><sup>1</sup> and COO− stretching band at 1631 and 1573 cm<sup>−</sup><sup>1</sup> [21,26]. LP depicts the C=O stretching at 1619 cm<sup>−</sup><sup>1</sup> and COO− stretching of amino band at 1400 cm<sup>−</sup><sup>1</sup> [20,37]. Next, similar spectra were shown by NDP cocrystals obtained from all solvents (methanol, ethanol, and acetone). It can be seen that the cocrystal spectra were different from PM in several bands between 4000 and 400 cm<sup>−</sup><sup>1</sup> regions of measurement.

Due to some overlapped bands, the second derivative spectra (Figure 3b) was generated to increase specificity by separating the overlapped bands on the similar region [37,38]. There are three focused areas shown in Figure 3, with the distinctive bands assigned by the wavenumber point and arrow.

**Figure 3.** *Cont.*

**Figure 3.** (**a**) FTIR spectra of diclofenac sodium hydrate (NDH), L-proline (LP), physical mixture 1:1 (PM), and the multicomponent 1:1 (NDP) from ethanol, methanol, and acetone. All NDPs have similar spectra, therefore only one of NDP spectra is marked on value of wavenumber changes. (**b**) The 2n<sup>d</sup> derivative FTIR spectra of NDP and PM. The blue number belongs to PM, and the black number reflects the NDP bands.

(**b**)

Figure 3b shows the broadband in the region of NDP at 2800–3700 cm<sup>−</sup>1, which was known as the position of –OH stretching from water and carboxylic groups [26,39]. The -OH water molecule bands of NDH have been previously reported to exist on 3200–3500 cm<sup>−</sup>1, coordinated with Na<sup>+</sup>, and interacted by the hydrogen bond to the other molecules [26]. The functional group's broadband at 3200–3750 cm<sup>−</sup><sup>1</sup> region also may involve –NH and NH–O stretching. Meanwhile, 1600-1750 cm<sup>−</sup><sup>1</sup> included –NH bend and –C=O stretching of carboxylic from both starting materials of the intermolecular bond [21,26,38–46].

In more detail, derivative spectra of PM and cocrystal in Figure 3b show that the new bands at 3598, 3667, and 3729 cm<sup>−</sup><sup>1</sup> of NDP replaced the 3687 cm<sup>−</sup><sup>1</sup> band of PM, which indicated the change in OH stretching. Next, here were new NDP bands at 2807 and 2861 cm<sup>−</sup><sup>1</sup> and the disappearing of 2827, 2526, and 2638 cm<sup>−</sup><sup>1</sup> bands from PM. These data revealed the change of –OH stretching of carboxylic of the two materials due to the cocrystal formation. In addition, the distinctive bands at 1620 cm<sup>−</sup><sup>1</sup> and 1677 cm<sup>−</sup><sup>1</sup> on the NDP spectra also support the new bonding formation.

The other changes revealed were the shifting of the C=O band at 1573 cm<sup>−</sup><sup>1</sup> to 1585 cm<sup>−</sup><sup>1</sup> and the amino stretching band from 1400 cm<sup>−</sup><sup>1</sup> to 1411 cm<sup>−</sup>1. This data reflected the alteration of COO− vibration of NDH and amino sidechains of LP [21,37,38]. A sharp band on 1334 cm<sup>−</sup><sup>1</sup> also supported the data of new interaction that involved –OH and C–O carboxylic. Besides, the changes of the 500–600 cm<sup>−</sup><sup>1</sup> band confirmed that –NH and CO moiety of LP contributed to composing the cocrystal. Therefore, overall, FTIR data supported a new solid structure construction, which was arranged by the carboxylate and amine from both starting materials, Na<sup>+</sup> ions from ND, and water molecules.
