# 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  
In order to investigate the drug permeation as a controlled release by the cross-linked PS gel swollen in limonene, ibuprofen was selected as a model drug (Figure 4). The drug was released through the rat skin into the receiver solution of pH 7.4 PBS at 37 \({}^{\circ}\)C using a [PERSON] diffusion cell as shown in Figure 4c. All PS gels swollen in limonene formulations show high potential releasing properties through the skin because limonene can enhance the permeation of the drug through the epidermis by increasing the activity of drug with SC or decrease the tortuous pathway in SC or both [14]. Nevertheless, the lack of solvent in PS-co-DVB would not be able to permeate drug in transdermal system. These exhibit the advantage of chemical organogel swollen in d-limonene could perform prolong release with simple preparation of cross-linked polystyrene. Permeability of drug from the PS gels swollen in limonene (Table 1, entry 1) was compared to the gel swollen in toluene (Table 1, entry 5) with the similar crosslinking condition (Figure 5a,e). Figure 4: (a) Chemical structure of Ibuprofen as model drug and d-limonene, photograph of in vitro permeation experiment by using Franz diffusion cell (b) and illustration of permeation study (c). Figure 5: In vitro cumulative release profile of ibuprofen from PS gel; Gel A (a), Gel B (b), Gel C (c), Gel D (d) and Gel E (e) (\(t=3\)). Toluene can be also defined as chemical enhancer for skin penetration [32]. However, it is extremely toxic and irritating to the skin, showing the merit of the present gels in limonene with the similar enhancer effect (Table 1, entry 1). The PS gels swollen in limonene A-D could prolong controlled release depending on the gel preparation conditions (Table 1, entries 1-4). Additionally, limonene has a low skin irritancy and it allows a reversible change in the skin structure when administered with a pretreatment method [18]. The permeability coefficient (\(KD/L\)) indicates the effect of the enhancer on the diffusion coefficient in SC, whereas the lag time decreases as the diffusion path length decreases. They are determined from Figure 5 and listed in Table 2. During the lag time period, SC would be conditioned for higher permeability and permeation reaches steady state after the lag time. Therefore, the decrease in lag time could also be due to fast SC conditioning times [8]. Gel A showed higher flux and the permeation coefficient as 53.1 \(\pm\) 0.03 \(\times\) 10\({}^{-4}\) cm/h (Table 2, entry 1) than that of gel B as 35.8 \(\pm\) 0.30 \(\times\) 10\({}^{-4}\) cm/h (Table 2, entry 2), influenced of the difference of the crosslinking ratios with 5% (Table 1, entry 1) and 10% (Table 1, entry 2), respectively. The same tendency was observed between gel C as 36.4 \(\pm\) 0.12 \(\times\) 10\({}^{-4}\) cm/h (Table 2, entry 3) and gel D as 17.9 \(\pm\) 0.20 \(\times\) 10\({}^{-4}\) cm/h (Table 2, entry 4) which were prepared both under 8 M with 5% (Table 1, entry 3) and 10% crosslinker (Table 1, entry 4), respectively. The concentration of gel preparation condition was also recognized compared with gel A as 53.1 \(\pm\) 0.03 \(\times\) 10\({}^{-4}\) cm/h (Table 2, entry 1) and gel C as 36.4 \(\pm\) 0.12 \(\times\) 10\({}^{-4}\) cm/h (Table 2, entry 3), which prepared with the same 5% crosslinking ratio (Table 1, entries 1 and 3). It is probably due to the cross-linked network structure of PS gel on activity through gel network. The mobility of drug solute in the skin is represented as D/L\({}^{2}\) diffusion parameter.