# Cationic Moieties in Polystyrene Gels Swollen with D-Limonene Improved Transdermal Delivery System
## 3 Results and Discussion
### Effect of Limonene as Chemical Enhancer and Density of the Network Structure on Permeability
It raised when increase the cross-linked degree, gel A as 0.10 \(\pm\) 1.03 h\({}^{-1}\) (Table 1, entry 1) and gel B 0.13 \(\pm\) 0.58 h\({}^{-1}\) (Table 1, entry 2) for 4 M and gel C as 0.05 \(\pm\) 1.06 h\({}^{-1}\) (Table 1, entry 3) and gel D 0.14 \(\pm\) 0.46 h\({}^{-1}\) (Table 1, entry 4) for 8 M.  
In order to clarify the relationship of permeability and gel network structure, the cross-linker ratio was plotted against to the steady flux of ibuprofen permeation through the skin (\(J_{\rm ss}\)) and elastic modulus (G') as shown in Figure S5. The steady flux decreased when the cross-linking degree and moduli increased for both concentration (4 and 8 M). Effect of the Cationic Moiety on the Controlled Release of Ibuprofen for Permeation through the Skin  
Since the sustainable controlled release is one of the concerning factors in drug delivery systems, it is important to fabricate controllable materials for TDD by organogels. The 4-vinylpyridine and (vinylbenzyl) trimethylammonium chloride were incorporated in order to control the permeation of drug through the skin by interacting with drug molecules. Figure 6 showed the plot of the released amount of the drugs against time and then the permeability (\(KD/L\)), diffusion parameter (\(D/L^{2}\)) and lag time were calculated as shown in Table 3. Upon the gradual increased introduction of 4 VP with 2 to 5%, the permeability of PS-4 VP gels was reduced significantly from 67.1 \(\pm\) 0.10 to 14.1 \(\pm\) 0.25 cm/h (Table 3, entries 1-5). Moreover, the lag time tended to increase together with the cationic interaction moiety while diffusion parameter (\(D/L^{2}\)) trend to decrease from 0.32 \(\pm\) 1.14 h\({}^{-1}\) to 0.04 \(\pm\) 0.93 (Table 3, entries 1-4). The increase in lagging time and the decrease in permeability and diffusion was attributed to the higher interaction of the cationic moiety with the drug molecules resulting in a controllable drug release. \begin{table}
\begin{tabular}{c c c c c c} \hline
**Entry** & **Gel** & **Flux\(J_{\rm ss}\) (\(\mu\)g/cm\({}^{2}\)-h)** & **Lag Time (h)** & **\(D/L^{2}\) (h\({}^{-1}\))** & **KD/L (\({}^{*}10^{-4}\) cm/h)** \\ \hline
1 & Gel A & 43.7 \(\pm\) 0.3 & 1.72 \(\pm\) 0.16 & 0.10 \(\pm\) 1.03 & 53.1 \(\pm\) 0.03 \\
2 & Gel B & 29.4 \(\pm\) 2.5 & 1.31 \(\pm\) 0.29 & 0.13 \(\pm\) 0.58 & 35.8 \(\pm\) 0.30 \\
3 & Gel C & 29.9 \(\pm\) 1.0 & 3.15 \(\pm\) 0.16 & 0.05 \(\pm\) 1.06 & 36.4 \(\pm\) 0.12 \\
4 & Gel D & 14.7 \(\pm\) 1.6 & 1.18 \(\pm\) 0.36 & 0.14 \(\pm\) 0.46 & 17.9 \(\pm\) 0.20 \\
5 & Gel E & 50.9 \(\pm\) 5.5 & 0.91 \(\pm\) 0.16 & 0.18 \(\pm\) 1.06 & 61.9 \(\pm\) 0.67 \\ \hline \end{tabular}
\end{table} 
Table 2: The skin permeation parameters of PS gel (gel A–D) and toluene gel (gel E). To emphasize the effect of interaction between drug and gel network structure, a stronger cationic moiety as ammonium salt was introduced as interaction unit in polymer chain in PS gel producing PS-VBAC gel. These interaction force of cationic moiety and ibuprofen (drug) was investigated by FT-IR in Figure S3,4. The VBAC was incorporated only 0.5 and 1 mol % due to poor solubility in d-limonene. However, it is not strong effect to lagging time and diffusion parameter, it was shown insignificantly difference of D/L\({}^{2}\); 0.07 \(\pm\) 0.40 h\({}^{-1}\) and 0.06 \(\pm\) 0.18 h\({}^{-1}\), respectively (Table 3, entries 6 and 7). Resulting in the small amount of cationic moiety is not effect to the mechanism of permeation through the stratum