## 3 Results and Discussion
### Stability Studies of Semi-Solid Formulations  
Tables 3 and 4 show the particle size values observed under the microscope immediately after formulation, and then, after 28 days (particle observations had been made at 7-day intervals). The observed changes after the four weeks were shown in the tables: Tables S1-S6. Among the different bases analysed in our study, Eucerin Ointment I is a popular compounding basis recommended for formulations with benzocaine [27]. For this reason, this base was selected to prepare our exemplary suspension-type ointments, without using the levigation process. Table 3 shows the particle size distribution of API in suspension-type formulations. Microscopic observations of the E-19 and E-20 formulations showed that prior levigation of benzocaine is necessary before its introduction to the base because the obtained formulations included benzocaine particles that exceeded the allowed size more than 2.5 times. As shown in Table 3, the size of API particles in the formulations of Eucerin Ointment I, after levigation, decreased significantly (\(p\leq 0.05\)). In addition, no particles with a diameter of >90 \(\upmu\)m were found. Figure 2: Pictures of selected ointments with benzocaine—after preparing them (**A**) and after 28 days (**B**). \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline \multirow{2}{*}{**Formulation**} & \multirow{2}{*}{**Time**} & \multicolumn{4}{c}{**Percentage of Individual Benzocaine Particles in the Sample (\%)**} & \multirow{2}{*}{_p_\(\leq\)} \\ \cline{3-3} \cline{5-6}  & **(Days)** & & **\textless{}30 μm** & **31–60 μm** & **61–90 μm** & **\textless{}91 μm** & \\ \hline \multirow{2}{*}{P-1} & after preparation & 72.5  
The study showed that the process of levigation and then mixing in a recipe mixer during the preparation of dispersible ointments significantly affects the change in the size of benzoaine particles in ointment formulations. In formulations in which an active substance was ground with base for a minimum of 5 min, a narrowing of the API size  
\begin{table}
\begin{tabular}{c c c c c c} \hline \multirow{2}{*}{**Formulation**} & \multirow{2}{*}{**Time**} & \multicolumn{3}{c}{**Percentage of Individual Benzocaine Particles in the Sample (\%)**} \\ \cline{3-6}  & & **\textless{}30 \(\upmu\)m** & **31–60 \(\upmu\)m** & **61–90 \(\upmu\)m** & **>91 \(\upmu\)m** \\ \hline P-E-29 & after preparation &  
distribution (over 82%) towards particle diameters below 60 \(\upmu\)m and the absence of particles was observed. Our study has revealed that the disintegration of benzoaine with a basis of 1.5 min is not sufficient to meet the pharmacopoeia requirements, with regard to the particle's size. For this reason, during our study, such a short levigation process of the active substance was terminated. There was a significant (\(p\leq 0.01\)) change in the percentage of API particles within the proposed size ranges in the formulations obtained immediately after preparation and after 4 weeks of storage. In formulations based on: Pentravan(r), Lekobaza LUX and Eucerin Ointment I, with the use of 5 min or 10 min grounding of benzoaine with the base, as well as in the case of the L-11 formulation, no particles with a diameter above 90 \(\upmu\)m were found throughout the study. The most optimal time of grinding of the active substance appears to be 10 min, which allows for obtaining relatively homogenous particles, with the smallest sizes. Prolongation of the levigation time, by a subsequent 5 min did not have any beneficial effect on the particle's size. Table 4 demonstrates the particle size distribution of API in emulsion-type formulations. The emulsion-type ointments, prepared on Lekobaza LUX, were the only ones to delaminate, making their observation under the microscope impossible. In the ointments, prepared on Pentravan(r) and Lekobaza, no precipitation of benzoaine crystals was noted throughout the study period.