*3.2. FTIR Spectroscopy and Solubility Measurements*

Figure 3 shows the FTIR spectra for all six new phases obtained in this investigation. FTIR provides a fingerprint sign of each compound and wealthy information about the noncovalent interactions between acceptor and donor groups. Peak shifts can be found in the bands of the functional groups involved in the hydrogen bonds, namely, the carbonyl –C=O functional group of the amine group of the lidocaine and lidocaine hydrochloride molecule and –OH groups in the polyphenol molecules. The shifts in lidocaine's –C=O

group stretching vibration occurred from 1661 cm−<sup>1</sup> to 1623–1620 cm−<sup>1</sup> for the new crystalline forms obtained, and from 1680 cm−<sup>1</sup> to 1677–1670 cm−<sup>1</sup> for lidocaine hydrochloride. These shifts demonstrate the hydrogen bonding between the –C=O group of lidocaine molecules and the –OH groups of the polyphenols [7], which as further confirmed by the structure solution.

**Figure 2.** Stability in ageing conditions (40 ◦C and 75% relative humidity) for the three **(lidhcl)** new forms.

**Figure 3.** FTIR spectra of (**a**) (**lid**) and (**b**) (**lidhcl**) multicomponent forms.

In order to measure the solubility of the new (lidhcl) forms, FTIR measurements were performed to avoid the overlapping observed in the UV spectra, due to the ability of FTIR to show us isolated peaks from each component, allowing us to construct a calibration curve with the intensity of an unambiguous peak of (lidhcl).

A calibration curve was built with different (lidhcl) concentrations [18,19] obtaining linear models with *R*<sup>2</sup> values greater than 0.99 (Figure 4), which were used to calculate the apparent solubility. The peak used for the calibration curves was the area between 1712 cm−<sup>1</sup> and 1612 cm−<sup>1</sup> corresponding to (lidhcl), where there was no interference of any of the used coformers.

**Figure 4.** Calibration curve of (**lidhcl**) concentrations ranging from 20 to 400 mg/mL.

The constructed calibration curve is shown in Figure 4, where the model's excellent agreement with the experimental concentrations can be appreciated. Each concentration was prepared and measured in duplicate to assure reproducibility, and the mean value is represented.

Table 2 presents the apparent solubilities calculated from FTIR data for each new (lidhcl) phase.

**Table 2.** . Solubilities in (mg/mL) of **(lidhcl)** multicomponent forms obtained from FTIR data.


The solubility decreased in the new phases with respect to reported values for **(lidhcl)** [9], generating **(lidhcl)** forms with an interesting path to modulate solubility.
