## 3 Results and Discussion
### In Vitro Assay Release
A comparison of profiles E-24 and E-E-36 confirmed the discrepancy between the formulations. The use of ethanol as a co-solvent for benzoaine led to different release profiles (\(f_{2}<50\)). Various mathematical models were used to investigate the kinetic model best fitted to the release data obtained (Table 6). From the value of the regression coefficient, the best-fit kinetic model was selected. It was shown that the _in vitro_ release of benzocaine from selected formulations had the highest R\({}^{2}\) values for [PERSON]'s model. The adjustment of the benzoaine release profiles from selected formulations to the [PERSON] model is at the level of 0.9830 to 0.9981. The release profile of the tested formulations was determined again after 28 days of storage at 20 \({}^{\circ}\)C-22 \({}^{\circ}\)C. There were no significant changes in the amount of the drug substance released to the acceptor medium. The kinetics of the release process also remained unchanged. Benzocaine, alongside lignocaine, is a frequently used local anaesthetic [23, 38, 39, 40, 41]. Its topical application is associated with a low risk of methaemglobinaemia, compared to other routes of administration [42]. The medium lipophilic nature of benzocaine requires the use of a suitable base, excipients, or absorption promoters. This paper analyzes the possibility of introducing a drug substance into the base by dissolving it in a co-solvent readily emulsifiable into the medium and preparing the drug as a suspension in the base. In this case, it is very important to use a base with emulsifying properties for drugs introduced at low concentrations. However, it should be noted that ethanol is an absorption promoter and therefore its use at higher concentrations is not recommended. In the absence of a suitable compatible solvent, it remains in pharmaceutical practice to disperse the drug as a suspension. This activity should be preceded by the process of levigation with a liquid miscible with the base or with the base itself. The literature provides different information with regard to the role of levigation in process of obtaining compounded prescription drug substances. For instance, in a study conducted by [PERSON] _et al._, manual setting of the Unguator(r) 2100 parameters allowed to obtain suspension-type ointments, with particle size in a range of 5-80 \(\upmu\)m, fulfilling in this way the pharmacopoeia requirements [1]. However, in a different study, [PERSON] and [PERSON] [43] have shown that salicylic acid, as another compounding substance, available in a form of relatively large crystals, before introduction to a base, should be levigated with liquid paraffin for at least 20 min. It has also been indicated that an active substance should not be disintegrated with ethanol, since this leads to the precipitation of crystals of salicylic acid, with particle size even up to 800 \(\upmu\)m. This result indicates another error that can occur in pharmaceutical compounding, during the preparation of suspension-type ointments. In studies conducted by [PERSON] _et al._[44], it was determined that a grinding time of ketoprofen (1 min or 5 min) does not have an influence on the size of crystals in the preparation. However, it was found that the independent variables, which could have an effect on a drug substances cation quality, include the time of mixing the ointment in a homogenizer, and the type of package in which a drug substance has been stored (_e.g._, tube/box). In other studies, [PERSON] _et al._[45] have indicated that the mixing of fluorocortisone acetate with proplyenic glycol, as a levigating substance, before its introduction to a base, has a beneficial influence on size, and equal dispersion of medication crystals in the ointment. Therefore, the selection of the levigating liquid and time of conducting levigation is determined by the physicochemical characteristics of the active substance, as well as the used equipment. API particle size is a critical parameter for many drug formulations.