## 4 Discussion
Taking into account all of the obtained results, it should be concluded that the DSC method is not the optimal tool for evaluating SLM formulation in terms of the content or incorporation of the active substance. Therefore, as already described, the presence of API and is impact on SLM properties in thermal studies can only be inferred indirectly, based on a decrease in the peak temperature associated with lipid melting (DSC) or the subtle change in the decomposition temperature (TG). As the results indicate, the spray drying process did not have any impact on the thermal properties of the tested microspheres with Compritol (Figure 6). Minor changes in the DSC and TG curves were mainly observed due to the use of additional excipients (like PVP or maltodextrin) in the spray drying process. However, the lipid forming the matrix of microspheres had a significant impact on the properties of the tested formulations. Compritol turned out to be resistant to the conditions of the drying process and stable during storage, in contrast to the less stable stearic acid, which sometimes undergoes unfavorable changes even at the initial stage of microsphere production [17; 19]. As in the case of the SLM dispersions, no peak of any of the tested active substances (CsA, Ind, SPIR) appeared in the DSC spectra of the spray-dried SLM. Comparing the DSC spectra of the microspheres with Compritol and stearic acid after spray drying, it can be concluded that stearic acid sometimes occurs in a less crystalline form in these samples (the intensity of the stearic acid peaks after spray drying was much weaker). Sometimes a similar effect in stearic acid was already observed at the stage of microsphere preparation. A lower degree of the crystallinity of the lipid matrix in SLM may be associated with higher encapsulation efficiency (which, however, was not observed), but also with a higher risk of instability. It is therefore possible to obtain microspheres characterized by unchanged thermal properties compared to placebo microspheres not only with Compritol, but also with stearic acid as a lipid forming the matrix of microspheres (Figure 7). The only problem in the production of SLM with stearic acid is the limited reproducibility of the process. The aforementioned shift in the melting point may be caused primarily by the interaction of active substances with lipids and other components of the dosage form, but also by polymorphic transformations of the components, the addition of other excipients or even the particle size. As it has been shown in earlier studies [19], the preparation of lipid microspheres using the hot emulsification method can proceed without or with a significant impact on the melting point of the matrices and their degree of crystallinity. This is mainly dependent on the lipid forming the SLM matrix, which has a major impact on the polymorphic transformations of the lipid matrix and the stability of lipid particles [29]. These results are consistent with those reported by [PERSON] et al. [21], which showed the stability of cetyl palmit (used to obtain the SLM) even after the heating process. The obtained results suggest that Compritol remains stable, while in SLM with stearic acid, changes are observed following melting and heating during the preparation of the SLM. DSC studies (Figures S3-S5) also confirm the previously described stability of SLM dispersions, in which the lipid matrix is composed of Compritol [20]. Certainly, the stabilizing effect of polysorbate on the properties of the lipid is not without significance. A similar effect has already been reported for polymer additives such as poloxamer, polyvinyl alcohol or polyvinylpyrrolidone, which may affect the polymorphism of the matrix [15]. Microspheres with stearic acid behave differently, they are not necessarily less stable during storage, but much more susceptible to changes occurring under the influence of production processes.