## 4 Discussion  
Transdermal drug delivery is a method for local or systemic treatment through the skin [32]. Transdermal drug delivery systems (TDDSs) include the reservoir system, matrix system, and microreservoir systems [17]. Matrix-type TDDSs are the most commonly used due to their simple design, ease of manufacturing, and good wear performance [33]. Matrix-type TDDSs have a low risk of accidental overdose and a low likelihood of drug abuse, making it the preferred choice for patients [34]. The SIM-CAP TDDS prepared in this study was designed as a matrix-type TDDS. Matrix materials are important for TDDSs. Hydroxypropyl methyl cellulose (HPMC) is considered the most important hydrophilic carrier material for the preparation of controlled drug delivery systems [35]. One of its most important features is high expansibility, which \begin{table}
\begin{tabular}{c c c} \hline \hline
**Parameters** & **Oral Administration** & **SIM-CAP TDDS** \\ \hline C\({}_{\text{max}}\) (ng/mL) & 12,503.50 \(\pm\) 952.10 & 11,762 \(\pm\) 535.87 \({}^{*}\) \\ T\({}_{\text{max}}\) (h) & 1 & 4 \({}^{*}\) \\ AUC\({}_{\text{(0-t)}}\) (ng:h\({}^{-1}\cdot\)mL\({}^{-1}\)) & 46,858.18 \(\pm\) 7563.52 & 110,192.83 \(\pm\) 7103.89 \({}^{*}\) \\ MRT (h) & 5.34 \(\pm\) 1.02 & 9.29 \(\pm\) 0.59 \({}^{*}\) \\ F (\%) & - & 235.16 \\ \hline \hline \end{tabular} \(C_{\text{max}}\): peak concentration; AUC: area under drug time curve; MRT: mean residence time; F (%): the calculated relative bioavailability is AUC(=0 for the TDDS/AUC(0=0 for the oral administration; \({}^{*}\)\(p<\) 0.05, compared with oral administration.  
\end{table} 
Table 7: Pharmacokine parameters (\(n=6\)). Figure 8: Plasma drug concentration–time curve analysis in rabbits after SIM-CAP TDDS and oral application (mean \(\pm\) SD, \(n=6\)); \({}^{*}\)\(p<\) 0.05 vs. oral administration. \begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**Administration**} & \multicolumn{2}{c}{**Erythema**} & \multicolumn{2}{c}{**Edema**} \\ \cline{2-4}  & **0 h** & **48 h** & **0 h** & **48 h** \\ \hline Blank patch & 0.00 \(\pm\) 0.00 & 0.24 \(\pm\) 0.04 & 0.00 \(\pm\) 0.00 & 0.14 \(\pm\) 0.01 \\ SIM-CAP TDDS & 0.00 \(\pm\) 0.00 & 0.36 \(\pm\) 0.08 & 0.00 \(\pm\) 0.00 & 0.23 \(\pm\) 0.05 \\ \hline \hline \end{tabular}
\end{table} 
Table 8: Skin irritation scores for blank patches and SIM-CAP transdermal patches (\(n=6\)). has a significant impact on the release kinetics of incorporated drugs [36]. HPMC is widely used due to its advantages such as wide availability, ease of use, good biocompatibility, strong film-forming ability, and good biodegradability [24]. Ethyl cellulose (EC) is a non-allergic and nontoxic polymer with excellent properties for the formation of tough films [37]. Carboxyl methyl cellulose (CMC-Na) is an anionic derivative of carboxymethyl cellulose that exhibits good biocompatibility and stable water solubility [38]. It has swelling properties and uniform viscosity and has been widely used in local drug formulations to achieve controlled and sustained targeted drug delivery [39; 40]. Polyvinylpyrrolidone (PVP) is a non-ionic water-soluble linear polymer widely used in cosmetics and pharmaceuticals because of its good solubility, excellent affinity for resins and polymers, biodegradability, nontoxicity, and compatibility [41]. Polyvinyl alcohol (PVA) has been widely used in biomedical and pharmaceutical applications due to its good biocompatibility, nontoxicity, hydrophilicity, and ability to form nanofibers and hydrogels [42; 43]. In this study, we used an orthogonal experimental table to verify the cumulative release of the two-polymer combinations. The results showed that when both the main and secondary matrix skeleton materials were made of PVA, the cumulative drug release was higher. Therefore, PVA was selected as the matrix skeleton material for the SIM-CAP transdermal patches. The skin, particularly the cuticle, forms an effective barrier to drug penetration, making it difficult to deliver drugs from the patches across the skin.