## 3 Results and Discussion
### In Vitro Assay Release
[PERSON] _et al._ observed that the API particle size in ointment formulations affects its homogeneity. In addition, the viscous nature of the base may hinder the reduction of API particle size [46; 47; 48]. The action of a high shear force during the milling or mixing process allows a significant reduction in API particle size compared to that of the original drug substance [47; 48; 49]. The use of a recipe mixer for the formulation of ophthalmic ointments resulted in a reduction of API particles from 19 \(\upmu\)m to 4 \(\upmu\)m [50]. Using ethanol, as a volatile solvent, is related to a risk of its evaporation that in consequence may lead to the precipitation of crystals of the active substance. In our study, this phenomenon was observed in emulsion-type ointments, prepared on: Eucerin Ointment I, Nourivan(tm) Antiox, and Fitalite(tm). Crystals of benzocaine were observed only after a week of storing such a formulation, and the precipitation of crystals has been increasing with time. Moreover, precipitation of the crystals (_e.g._, higher amounts and larger sizes) occurred in the ointments that were more intensely homogenized in Unguator(4 min, 1630 rpm) compared to the ones that were mixed, using lower working parameters of the mixer (2 min, 1260 rpm). Most probably, a reason for this is the stronger warming of a sample, connected with accelerated evaporation of the alcohol. In emulsion-type ointments, prepared on Pentravan(r) and Lekobaza, during a period of 4 weeks, there was no precipitation of active substance that could be caused by the properties of these bases. In the case of Pentravan(r) which contains liposomes, benzocaine could be packaged into nano-carriers. In Lekobaza--a composition and/or structure having limited ethanol evaporation. However, it should be pointed out that in the creams prepared on Lekobaza, despite a lack of benzocaine crystals (from the 3 rd week), the microscopic appearances of the bases have changed, indicating a necessity to discard these formulations. In the available literature, no particular reasons were mentioned for the phase separation of emulsion-type ointments, prepared on Lekobaza LUX. However, characteristics of this basis, and in particular, the presence of emulgators could contribute to the observed discrepancy. Pentravan(r) is a new compounding base that requires careful observation in the process of preparing various formulations. Its characteristics (emulsion o/w) [4] and the presence of liposomes cause doubt about whether or not the preparations manufactured on such a base can be safely homogenized in a mechanical mixer, without a negative impact on the medication's therapeutic effects. Although studies conducted by [PERSON] _et al._[51] were relevant to a method of obtaining emulsion, they revealed that the parameters of mixing have an influence on the rheologic properties of the obtained products (since emulsions during the mixing process are exposed on high shearing forces, which can negatively influence their internal structure). Based on the results of our study, we concluded that the parameters of mixing should be individually selected for a given type of emulsion, in order to provide an appropriate grinding, which in turn, translates to stability and quality of the preparation. The study of the release of benzocaine from selected bases can facilitate the selection of the appropriate medium depending on the skin condition. Absorbent lipophilic bases are indicated for use on dry skin after alleviating inflammation. A contraindication for this type of base is exudative states. However, skin with excessive secretion of sweat or sebaceous glands better tolerates water-washable creams of an o/w emulsion nature. Diseased skin shows increased sensitivity to irritants or allergizing factors. Therefore, the preparation of formulations for the individual needs of the patient, depending on the skin condition, requires both sensory testing and release and retention rates.