*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.


2.2.7. Anti-Photoaging Effect

Photoaging is a result of chronic ultraviolet irradiation, which is one of the most harmful environmental factors affecting the skin. Recently, studies on marine compounds as safe anti-photoaging alternatives have been published by Hwang et al. [23]. They reported that fucosterol obtained from the brown alga *Sargassum fusiforme* was observed to have anti-photoaging properties. Fucosterol therapy decreased ultraviolet B (UVB)- induced production of matrix metalloproteinase-1 (MMP-1), IL-6, p-c-Jun, and p-c-Fos and increased type I and transforming growth factor-1 (TGF-1) procollagen expression in normal human dermal fibroblast cells. In addition, fucosterol derived from *Sargassum fusiforme* was observed to regulate the expression of MMPs and type-I pro-collagen in UVirradiated HaCaT cells by modulating, microtubule associated protein kinase (MAPK) [45]. These findings suggest that fucosterol extracted from *Sargassum fusiforme* is a potential candidate for the prevention and treatment of skin aging.