*4.2. Mobility of Hazardous Elements*

The presence in a product of an elemental impurity will have safety concerns only once released, with different mechanisms underlying the release of each particular element, mainly depending on its position in the structure of the hydrogel components. Nevertheless, it is possible to calculate a parameter of general comparative interest; mobility of the elements from the dosage form. The mobility of an element could be calculated as the ratio between the element content/element released.

In view of the previously shown results, the mobility of hazardous elements from ALIPS9 and ALIG30 hydrogels was minimal in the major part of the cases (Figure 3). These results could be explained by the high adsorption capacity of palygorskite and sepiolite clay minerals, their low cation exchange capacity, and the gel network of hydrogels. The mobility of tracers has been explained due to the formation of inner-sphere complexes with clay and other associated mineral surfaces [75–77]. It also seems clear that different ionic equilibriums are established through time in both hydrogels (Figure 4). For instance, Co, Ba, and Sn reduce their mobility while As and Cd increase it, thus demonstrating that elements established different equilibriums within the hydrogel.

**Figure 3.** Element mobility (%) versus the total amount of element in ALIPS9 (**A**) and ALIG30 (**B**). Only mobile elements are shown.

**Figure 4.** Spider diagram of element mobility. Only mobile elements are shown. The logarithmic scale was used, though not included in the spider diagram for simplicity and clarity.

Sn showed to be the most mobile element, followed by Cu (Figure 3). Sn was not detected in ALI, which indicates that the release of this element came from PS9 and G30. On the other hand, Cu was detected in the three ingredients. In ALIPS9, the third element with significant mobility was Mo (Figure 3A). Molybdenum was also detected as an element with remarkable mobility in ALIPS9, while the mobility in ALIG30 was significantly smaller. The differences in Mo amounts released (Table 3) could be ascribed to the differential solid-liquid equilibrium established within both hydrogels since both PS9 and G30 presented the same amount of this element (Table 2). The reduction of Mo mobility in ALIG30 indicates that the G30 clay mineral has a better ability to retain the Mo in ALI.

Li, Ba, V, and Cd were the elements with the smaller mobility. V was not detected in ALI, which means that the released amount was due to the clay minerals. V and Li did not participate in the solid-liquid equilibrium established between solid and liquid phases since their mobility was constant with time. Although Ba was an element with minimal mobility, it reduced with time in both hydrogels. The fact that G30 showed higher Ba amount than PS9 together with the fact that Ba mobility in this hydrogel was smaller than in ALIPS9 indicates that it is a structural element of G30. Moreover, the similar release of Ba from ALIPS9 and ALIG30 means that, probably, the major part of the Ba released came from ALI instead of PS9 and G30.

Cd and As were slightly mobile, with higher results in the case of ALIG30 hydrogels. The absence of Cd mobility in ALIPS9 was due to the extremely low amounts detected in PS9 and its absence in ALI. On the contrary, G30 possessed higher amounts of Cd (Table 2), which explains the mobility results (Table 3). Cd and As were the most crucial elements determining the safety of the hydrogels. It is worth to mention that, with respect to the As and Cd amounts and mobility, ALIPS9 hydrogels could be considered the safest formulation.

The mobility of Sn, Cu, Mo, and Ba from hydrogels reduced as time passed. The mobility reduction could be explained by the irreversible adsorption of the elements by PS9 and G30. In fact, fibrous clay minerals have been proposed as environmental remediation ingredients and wastewater treatments aiming to eliminate heavy metals with promising results [78–81].

The spider diagram (Figure 4) clearly shows that, as a general trend, palygorskite hydrogels reduced the mobility of hazardous elements with time (with a reduction in area), whereas this was not obvious for sepiolite hydrogels.

Finally, previous studies on elemental mobility from clay minerals, spring waters, and thermal muds have reported that the amount of released elements highly depends on their concentration in spring water, the release of elements from the solid phase being negligible [9]. Nonetheless, in view of the results of the present study suggest that solid-phase composition did play a crucial role. This discordance could be due to the high structuration of the present hydrogels.

At this point of the study, and looking at the safe dose calculations (Table 4), the way to guarantee the absence of any intoxication risk would be to apply the hydrogels locally (over restricted areas of the skin, wounds, joints, etc. That is, hydrogel bath treatment should be avoided if potentially toxic doses of the elemental impurities want to be minimized. Nonetheless, bioavailability and percutaneous permeation studies would be highly useful and valuable to establish safe usage guidelines for these formulations.
