## 2 Materials and Methods
### Methods  
#### 2.2.1 Formulation of the Ointment  
Ointment formulations with benzocaine (2% wt/wt) were prepared on a total of six ointment bases, including three new, multiphase (Pentravan(r), Nourivan(tm) Antiox, and Fitalite(tm)) and three known (Lekobaza, Lekobaza LUX, and Eucerin Ointment I) used in pharmacies, using the prescription mixer (Unguator(r) E/S; Gako GmbH, Scheslitz,Germany). Benzocaine was introduced into the base in two combinations: by grinding it in a mortar with an equivalent small amount of the base (levigation) or by dissolving it in ethanol. _Formulation of ointments of the suspension type_  
The composition of suspension-type ointments and their methods of formulation are shown in Table 1.  
Formulations in the form of suspensions were obtained after grinding the drug substance in a mortar with an equivalent amount of the vehicle. Various grinding times were used in the levigation process: 1.5, 5, 10, and 15 min. The remaining amount of the base \begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{\
\begin{tabular}{c} **Formulation** \\ **Code** \\ \end{tabular} } & \multirow{2}{*}{
\begin{tabular}{c} **Qualitative Composition of Prepared** \\ **Ointment** \\ \end{tabular} } & \multicolumn{2}{c}{**Technical Parameters**} \\ \cline{3-5}  & & & **Time** & **Levigation (min)** & **Mixing Time (min); Agitator** \\ \hline P-1 & Pentravan\({}^{\circledR}\) & Benzocaine & 1.5 & 2; 1260 \\ \hline P-2 & Pentravan\({}^{\circledR}\) & Benzocaine & 1.5 & 4; 1630 \\ \hline P-3 & Pentravan\({}^{\circledR}\) & Benzocaine & 5.0 & 2; 1260 \\ \hline P-4 & Pentravan\({}^{\circledR}\) & Benzocaine & 5.0 & 4; 1630 \\ \hline P-5 & Pentravan\({}^{\circledR}\) & Benzocaine & 10.0 & 2; 1260 \\ \hline P-6 & Pentravan\({}^{\circledR}\) & Benzocaine & 10.0 & 4; 1630 \\ \hline P-7 & Pentravan\({}^{\circledR}\) & Benzocaine & 15.0 & 2;1260 \\ \hline P-8 & Pentravan\({}^{\circledR}\) & Benzocaine & 15.0 & 4; 1630 \\ \hline L-9 & Lekobaza & Benzocaine & 5.0 & 2; 1260 \\ \hline L-10 & Lekobaza & Benzocaine & 5.0 & 4; 1630 \\ \hline L-11 & Lekobaza & Benzocaine & 10.0 & 2; 1260 \\ \hline L-12 & Lekobaza & Benzocaine & 10.0 & 4; 1630 \\ \hline L-13 & Lekobaza & Benzocaine & 15.0 & 4; 1630 \\ \hline LLux-14 & Lekobaza LUX & Benzocaine & 5.0 & 2; 1260 \\ \hline LLux-15 & Lekobaza LUX & Benzocaine & 5.0 & 4; 1630 \\ \hline LLux-16 & Lekobaza LUX & Benzocaine & 10.0 & 2; 1260 \\ \hline LLux-17 & Lekobaza LUX & Benzocaine & 10.0 & 4; 1630 \\ \hline LLux-18 & Lekobaza LUX & Benzocaine & 15.0 & 4; 1630 \\ \hline E-19 & Eucerin Ointment I & Benzocaine & - & 2; 1260 \\ \hline E-20 & Eucerin Ointment I & Benzocaine & - & 4; 1630 \\ \hline E-21 & Eucerin Ointment I & Benzocaine & 5.0 & 2; 1260 \\ \hline E-22 & Eucerin Ointment I & Benzocaine & 5.0 & 4; 1630 \\ \hline E-23 & Eucerin Ointment I & Benzocaine & 10.0 & 2; 1260 \\ \hline E-24 & Eucerin Ointment I & Benzocaine & 10.0 & 4; 1630 \\ \hline N-25 & Nourivan\({}^{\text{TM}}\) Antiox & Benzocaine & 1.5 & 2; 1260 \\ \hline N-26 & Nourivan\({}^{\text{TM}}\) Antiox & Benzocaine & 1.5 & 4; 1630 \\ \hline F-27 & Fitalite\({}^{\text{TM}}\) & Benzocaine & 1.5 & 2; 1260 \\ \hline F-28 & Fitalite\({}^{\text{TM}}\) & Benzocaine & 1.5 & 4; 1630 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: The composition of suspension-type ointments with benzoaine and technical parameters of their preparation methods. was added in portions to the thus obtained benzoaine concentrate and thoroughly mixed until a homogeneous consistency was obtained. Then the whole was transferred to the container, which was mounted in the Unguator(r) and the appropriate mixing parameters were set: mixing time/agitator rotation, respectively: 2 min/1260 rpm or 4 min/1630 rpm. _Formulation of emulsion-type ointments_  
Benzocaine was dissolved in ethanol 96% in a ratio of 1 to 8. After the API was completely dissolved, the solution was added to a container with a pre-weighed base. The whole was homogenized in a recipe mixer, setting the parameters described above.