**4. Discussion**

The investigation of the collected data has revealed a contradiction between the results of the chemical analysis concerning the curcumin content in the samples and those of the other characterizations which did not clearly indicate the presence of CR in the solids except the one obtained by reconstruction with CR-ethanolic solution (RZn3Al-CR(Et)). A possible explanation for this inconsistency is revolving around the CR-loading present in the solids, which was calculated based on the determination of the total organic carbon content, including also the carbon from the compounds obtained by the degradation of curcumin during the syntheses performed at basic pH. Several studies concerning the stability of curcumin in the alkaline medium have suggested that the degradation products are ferulic acid, feruloyl methane, vanillin and

*trans*-6-(4'-hydroxy-3'-methoxyphenyl)-2,4-dioxo-5-hexenal [2,7,8,43,44]. The results of our DR-UV–Vis analysis (Figure 7) confirmed the presence of feruloyl methane and ferulic acid in the samples obtained by co-precipitation PZn3Al-CR(Aq), PZn3Al-CR(Et), while in the sample RZn3Al-CR(Aq) only the presence of feruloyl methane was evidenced. This fact implies that when curcumin is contacted with an aqueous solution containing NaOH, the main degradation product resulted is feruloyl methane and that ferulic acid is obtained most probably during the ageing of the precipitates. Our findings are in agreemen<sup>t</sup> with those of Gordon and Schneider [43], which showed that vanillin and ferulic acid were not the major degradation products of curcumin.

From the results of DR-UV–Vis, it could also be inferred that the degradation of curcumin was less pronounced when the co-precipitation was performed with CR-ethanolic solution since the spectrum of PZn3Al-CR(Et) showed a more intense absorption in the region 400–600 nm compared to the spectrum of PZn3Al-CR(Aq). This fact could be due to the formation of a CR-Zn(II) complex which according to literature data has the maximum absorption in the visible region at 455 nm [42]. The presence of such a complex was also suggested by the ATR-FTIR spectrum of PZn3Al-CR(Et) (Figure 5a) displaying an absorption maximum at 1550 cm<sup>−</sup>1. The red shifting of the absorption maximum specific to CR-Zn(II) complex from 1583 cm<sup>−</sup><sup>1</sup> [42] to 1550 cm<sup>−</sup>1, could be related to its distortion under the influence of the LDH matrix and/or to its participation as secondary layered phase (whose presence was indicated by XRD analysis) in the LDH structure. The ATR-FTIR spectrum of the sample RZn3Al-CR(Aq) (Figure 5b) showed a sensibly weaker absorption band specific to CR-Zn(II) confirming that the stabilization of curcumin by complexation with Zn(II) was much lower in this case, most probably due to its degradation during the dissolution in the aqueous alkaline solution. The degradation of curcumin during the co-precipitation and reconstruction with alkaline aqueous CR-solution could also explain why the XRD patterns of the samples PZn3Al-CR(Aq) and RZn3Al-CR(Aq) did not show the specific di ffraction lines of CR. The lower degradation of CR during the preparation of the PZn3Al-CR(Et) solid accompanied by the formation of the CR-Zn(II) complex evidenced by ATR-FTIR could be responsible for the obtaining of the extra layered phase with slightly larger interlayer space and a degree of crystalline disorder along the c-axis revealed by the XRD analysis (Figure 4a). Even if both ATR-FTIR and DR-UV–Vis spectra of the sample RZn3Al-CR(Et) obtained by reconstruction with CR-ethanolic solution indicated the presence of curcumin, its presence was not evidenced as a single phase in the XRD pattern most probably because nano-particles of curcumin were dispersed on the surface of this solid which contained also nano-sized particles of ZnO (see Table 2). Considering the results of the characterization studies it may be concluded that curcumin was incorporated without degradation only in RZn3Al-CR(Et), while in the rest of the solids, CR-Zn(II) complex and di fferent degradation products of curcumin were incorporated in various extents. The amount of curcumin released from the synthesized solids was higher for those prepared with CR-ethanolic solutions (e.g., RZn3Al-CR(Et) and PZn3Al-CR(Et)) (Figure 8) and was well correlated to the content of the stabilized curcumin in the samples.

The release of curcumin from the CR-loaded solids was significantly influenced by the pH of the bu ffer solution utilized in the "in vitro" release studies. The bu ffers with acid pH (1, 2 and 5) allowed a better release of curcumin than the neutral to basic pH bu ffers (pH 7 and 8) which have a significant degrading e ffect on curcumin as it was indicated by Wang et al. [45]. This fact suggests that curcumin will be better released in the stomach where the pH can vary in the range 1.5–6.5 (e.g., pH 1.5–4.0 in the lower portion of the stomach and pH 4.0–6.5 in the upper portion of the stomach where predigestion takes place), than in the duodenum where the pH changes from 7.0 to 8.5 [46,47]. Considering the results of the CR-release tests (Figure 8) it may be inferred that CR-release will be lower in the upper portion of the stomach where the pH is less acidic (release tests at pH 5) and will enhance gradually as the solid will reach the lower portion of the stomach (release tests at pH 2 and pH 1), and it will be negligible when the solid reaches the duodenum (release tests at pH 7 and pH 8).
