## 3 Results and Discussion
### Dissolution Test Results and Korsmeyer-Peppas Release Kinetics  
Figure 6 demonstrates the in vitro % release of MLT from the formulations F1-F16 and the commercially available drug Circadin(r) vs. time. Table 3 presents the similarity factor (f\({}_{2}\)) analysis results for % release, comparing all formulations with the commercial product Circadin(r). Dissolution profiles are considered similar when 50 \(\leq\) f\({}_{2}\) < 100, with F1, F6, F9, F11, F12, F13, and F14 meeting this criterion. The Korsmeyer-Peppas equation fitting results, are shown in Table 4. The release data showed a good fit with the Korsmeyer-Peppas equation \(R^{2}\) values ranging between 0.85 and 0.98. The dissolution profile of MLT from the F1 and F3 formulations (Figure 6a), at pH 4.5, is similar. F1, containing the polymeric excipient neat PLA, and F3, comprised of the polymeric material PLA-glycerol, show at t = 2 h, ca. 43.6% MLT release, almost identical to the commercially available drug, Circadin(r). This release profile similarity trend, between F1 and F3, is continued and at t \(\geq\) 2 h, reaching quantitative release at t = 7 h. This modified MLT release from the F1 and F3 formulations could find application in patients facing sleep onset and mainly sleep maintenance problems. From the F2 (PLA-sorbitol) and F4 (PLA-pentaerythntol) formulations, MLT is released, at t = 2 h, at 81.3% and 62.4%, respectively. The much higher release of MLT from the F2 formulation mirrors the \begin{table}
\begin{tabular}{c c c} \hline
**Formulation** & \(\mathbf{\mathit{n}}\) & \(\mathbf{K_{KP}}\) & \(\mathbf{R^{2}}\) \\ \hline F1 & 0.74 & 1.20 & 0.98 \\ F2 & 1.88 & 0.01 & 0.98 \\ F3 & 0.69 & 1.66 & 0.96 \\ F4 & 0.55 & 4.67 & 0.92 \\ F5 & 0.86 & 0.41 & 0.98 \\ F6 & 0.54 & 3.11 & 0.96 \\ F7 & 0.66 & 1.31 & 0.94 \\ F8 & -* & -* & -* \\ F9 & 0.67 & 1.51 & 0.96 \\ F10 & -* & -* & -* \\ F11 & 0.5 & 4.1 & 0.96 \\ F12 & 0.57 & 2.61 & 0.98 \\ F13 & 0.63 & 2.07 & 0.85 \\ F14 & 0.85 & 0.54 & 0.94 \\ F15 & 0.67 & 2.16 & 0.95 \\ F16 & 0,6 & 2.88 & 0.96 \\ Circadin® & 0.47 & 4.77 & 0.92 \\ \hline \end{tabular} \({}^{\star}\) values could not be calculated.  
\end{table} 
Table 4: Korsmeyer–[PERSON] equation fitting results. \begin{table}
\begin{tabular}{c c} \hline
**Formulation** & \(\mathbf{\mathit{f_{2}}}\) \\ \hline F1 & 53.17 \\ F2 & 29.43 \\ F3 & 49.40 \\ F4 & 34.02 \\ F5 & 38.93 \\ F6 & 64.78 \\ F7 & 44.36 \\ F8 & 34.26 \\ F9 & 57.42 \\ F10 & 43.19 \\ F11 & 66.38 \\ F12 & 65.07 \\ F13 & 59.23 \\ F14 & 53.11 \\ F15 & 42.87 \\ F16 & 49.27 \\ \hline \end{tabular}
\end{table} 
Table 3: The similarity factor (f\({}_{2}\)) results. influence on the MLT release due to the presence of six hydroxy-groups in the PLA-sorbitol derivative, instead of the four hydroxyls in the PLA-pentaerythnitol F4 formulation. The higher the number of OHs, the higher is the MLT release from the formulations, due to enhanced hydrogen bond formation mainly between the C5-OMe H-bond acceptor moiety in melatonin and the H-bond donor OH groups in the PLA-sorbitol derivative; this leads to a more favourable aqueous dissolution of MLT from the F2 formulation. It is known, that the higher the number of hydroxyl groups in excipients, the better are the solubility and dissolution rates of the APIs via hydrogen bonding interactions (Figure 7), [57, 58]. Thus, in view of this, formulations F2 and F4, and especially F2, could provide satisfactory treatment for patients with sleep onset problems. According to the obtained data, in terms of the MLT release kinetics, the formulations F1, F3, and F4 exhibited a non-Fickian or anomalous diffusion mechanism (0.45 < n < 0.89), indicating a combination of simple diffusion and polymer relaxation (Case II diffusional transport). This behavior suggests that the release of MLT is influenced by both drug diffusion through the matrix and the polymer's swelling or relaxation process, which is characteristic of non-Fickian transport [59].