*3.3. X-ray Diffraction*

Powder X-ray diffraction patterns are a distinctive fingerprint of the crystalline phases. It can be confirmed from Figure 5 how the PXRD patterns of the new **(lid)** and **(lidhcl)** phases were entirely different from the starting API, ensuring the appearance of new crystalline phases. Additionally, the comparison of the simulated PXRD data from SCXRD solved structures with the observed patterns obtained for each bulk powder obtained from LAG experiments could confirm the new obtained phases (Figure S1).

From the single crystals obtained for each new phase, structure solutions were achieved, and these structures were analysed to extract information that could relate stability to the structure.

Cocrystals of lidocaine free base **(lid**) with two di-hydroxy isomers (hydroquinone, **hq** and resorcinol, **res**) and one tri-hydroxybenzene (pyrogallol, **pyr**) coformer were cocrystallised, and their crystal structure was determined. To evaluate the effect of the chloride ion on the stability and properties performance of lidocaine multicomponent solid forms,

analogue cocrystals were also obtained using lidocaine hydrochloride salt **(lidhcl)**. The structural features of both free base and ionic lidocaine systems are discussed in this section.

**Figure 5.** PXRD patterns of (**a**) **(lid)** and (**b**) **(lidhcl)** new multicomponent forms.
