*3.3. Photochemical Characterization*

Spectrophotometric measurements gave insight into the radiation frequencies absorbed by the drug and its intercalated compound and could be used to achieve information on the photostability of the materials. The absorption spectrum of crystalline KET in acid form (KETH) presented a maximum at 280 nm and a broad and structured band in the 320–390 nm (Figure 3). Deprotonation of the drug did not change its absorption spectrum; in fact, the KET-Na (Figure 3) showed a spectrum very similar to that obtained for KETH, probably because the acid functionality is not conjugated with the chromophoric moiety. On the other hand, the spectrum of the intercalated sample ZnAl-KET showed the main band centered at 280 nm and a shoulder without any structures at about 330 nm (Figure 3). The different spectra recorded for KET-Na and ZnAl-KET indicated that the interactions with the inorganic matrices and/or the interactions between chromophores modified the electronic distribution in the drug.

**Figure 3.** Absorption spectra of crystalline KET in acid form (KETH) (black line), KET-Na (blue line), and ZnAl-KET (red line).

The spectrophotometric analysis conducted on the samples under investigation before and after irradiation at 330 nm enabled us to evaluate and compare their photostability. In all cases, after 2 h of irradiation, the optical density changed (ΔOD) in the 250–400 nm range and was detected even if the relative variations were different (Figure 4). In particular, KET showed a smaller variation, compared to the other samples, in the whole spectral range investigated (black line Figure 4, Table 1). This behavior indicated that KETH had a higher photostability, in agreement with the literature data [26], where the photodecomposition of ketoprofen is reported to be pH-dependent, and a higher photodegradation is observed when the drug is in the anionic form. Therefore, KETH was not a good reference for the intercalated samples. KET-Na showed a remarkable increase in the absorption upon corresponding irradiation (blue line Figure 4, Table 1); this indicated that the deprotonated drug had a photostability lower than KETH, also when in powder form. Since the drug was intercalated in an anionic matrix, KET-Na was considered a good reference for assessing the photochemical behavior of the intercalation compound.

**Figure 4.** Absorption spectra of KETH (black line), KET-Na (blue line), and ZnAl-HTlc-KET (red line) before and after 120 irradiation at 330 nm.

When ZnAl-KET was exposed to the 330 nm radiation (red line Figure 4) in the same experimental conditions, a decrease in the absorption at wavelengths below 360 nm was observed, while at longer wavelengths, an increase in optical density was detected. This behavior suggested that the drug underwent different photochemical processes in the inorganic matrix. However, the optical density changes of the intercalation compound were small compared to those observed for KET-Na, as shown by the data reported in Table 1.


**Table 1.** ΔOD measured at different λobs upon 2 h irradiation of the samples at 330 nm.

ΔOD: optical density changes; λobs: observation wavelengths

The comparison of the data suggested that the hybrid ZnAl-HTlc was able to photoprotect the deprotonated form of KET. The photoprotection mechanism can be due to a physical filter effect and to a modification of the photochemical reaction paths. Indeed, it has been reported that KET carboxylate excitation produces mainly the triplet state, which undergoes a rapid and efficient photodecarboxylation reaction [27]. The intercalation in the layered solid could reduce the efficiency of the decarboxylation step due to space confinement of the species.
