## 3 Results and Discussion
### In Vitro Assay Release  
The release profiles of benzoocaine from selected ointments into the buffer solution are presented in Figure 3. In the _in vitro_ drug release study from semi-solid ointments, it was shown that most of the drug substance--26.26%, was released from the E-E-36 formulation. Subsequently, from the remaining formulations, 20.73% of the benzoaine was released from the P-6 formulation, 17.54% from P-E-30 and the least, 10.70% from E-24. It was shown that P-E-30 was characterized by a significantly slower release of the drug compared to P-6 (Table 6). It is probably related to the change in the specific surface of the drug and its \"packaging\" into liposomes present in Pentravan(r) [36]. This can be attributed to the interactions and chemical bonds between the benzoaine, the ethanol (co-solvent) and components of Pentravan(r), which contains a 20-30% Pluronic F127 solution as the aqueous phase and a mixture of lecithin and isopropyl myristate as the oil phase. The similarity coefficient value\(f_{2}\) obtained from comparing the release profiles of P-6 with P-E-30 was calculated to be 77.73. The authors suppose that dissolving benzoaine in ethanol and introducing it into the base could have changed its release from the transdermal base containing Lipoil. Perhaps the lack of co-solvent addition, combined with the medium lipophilic nature of the benzoaine particle, allowed the drug to be preserved in a nonionized form, in which the drugs have a higher penetrating ability than in the ionized form. [PERSON] _et al._ indicated that the lipophilic nature of the introduced particle has a greater possibility of being released from the hydrophilic base [37]. In addition, the pH of the formulation also influences the permeability, because depending on its value, weak acids and bases can be ionized, which is not always the desired effect, because neutral substances penetrate \begin{table}
\begin{tabular}{c c c c c c} \hline \hline \multirow{2}{*}{**Formulation Code**} & \multirow{2}{*}{**Cumulative Release Benzocaine, Q (\%)**} & \multicolumn{4}{c}{**Kinetics Release Models**} \\ \cline{3-6}  & & **Zero Order** & **First Order** & **Higuchi** & **k\({}_{\mathbf{H}}\)** \\  & & **R\({}^{2}\)** & **R\({}^{2}\)** & **R\({}^{2}\)** & **(\(\mathbf{\mu}\)g/cm\({}^{2}\) h\({}^{1/2}\))** \\ \hline P-6 & 20.73 \(\pm\) 0.51 & 0.9734 & 0.8468 & 0.9978 & 226.91 \\ \hline P-E-30 & 17.54 \(\pm\) 0.84 \({}^{\text{a}}\) & 0.9832 & 0.8526 & 0.9979 & 244.07 \({}^{\text{a}}\) \\ \hline E-24 & 10.70 \(\pm\) 0.45 & 0.9835 & 0.8629 & 0.9981 & 153.37 \\ \hline E-E-36 & 26.26 \(\pm\) 1.04 \({}^{\text{b}}\) & 0.9388 & 0.8363 & 0.9830 & 471.16 \({}^{\text{b}}\) \\ \hline \hline \end{tabular} \(\text{k}_{\text{H}}\)— average release rate, R\({}^{2}\)—regression coefficient, Statistically significant difference: \({}^{\text{a}}\)\(p\)\(\leq\) 0.01 with respect to P-6, E-E-36, \({}^{\text{b}}\)\(p\)\(\leq\)0.01 with respect to P-6, E-E-30; \(n\) = 6; M—mean; SD—standard deviation.  
\end{table} 
Table 6: Q factor, regression coefficient R\({}^{2}\) and fitting of mathematical models to the data of benzoaine release from selected ointments. Figure 3: _In vitro_ drug release profiles of four benzoaine semi-solid ointments: (**A**) formulations P-6, P-E-30, (**B**) formulations E-24, E-E-36. Mean \(\pm\) SD, \(n\) = 6.  
more easily. Therefore, in this case, further research is needed and is planned for the near future. The use of the preparation on the patient's skin is also important because the skin is rich in enzymes that can affect the metabolism of the drug itself. In addition, it should be remembered that the active substance used in the experiment may create pharmaceutical incompatibility with cationic compounds. In contrast, ointment E-24 exhibited a significantly lower release rate among all the tested formulations. The release process from benzocaine from this formulation was approximately three times slower compared to the E-E-36 formulation.