## 4 Discussion  
The thermal characteristics of the placebo and drug-loaded SLM (Table 1) in the form of a liquid dispersion or a spray-dried powder were investigated. Physical mixtures were tested for control purposes. The tested SLM formulations contained from 0.1 to 5.0% of the drug substance, depending on the type of substance. The content of the active substance, determined after preparation, was in each case in the range of 100.0 \(\pm\) 5%, which was considered the desired value. The detailed distribution of active substances in the individual phases of the SLM formulation has been discussed and characterized in previous reports [18,19]. Carrying out a DSC measurement of SLM dispersion requires proper sample preparation, because the presence of water in the sample during the analysis caused the DSC and TG curves to show a characteristic profile of water evaporation followed by thermal decomposition with carbonization. Only the DSC analysis of dry samples makes it possible to distinguish events related to lipid melting. Of course, this does not mean that the DSC/TG method is not suitable for testing SLM obtained in the form of liquid dispersions. Such microspheres are tested as a dry residue, and sample preparation becomes crucial. The most important thing is that the method of drying the sample must not affect the properties of the microspheres studied at the analysis stage. Pre-heating the sample (e.g., a few minutes at 80 \({}^{\circ}\)C) and then cooling it down again before analysis is one of the recommended methods [13,21]. However, it should be taken into account that this process, taking place at a temperature above the lipid melting point, will certainly affect the properties of the formulation. Another method is to lyophilize the dispersion before thermal analysis. Different drying processes can lead to significant changes in the properties of the sample as a result of the effect of temperature (both increased and decreased during freeze-drying) [22], not to mention other adverse forces acting on the microspheres during freezing. In order to avoid preheating before the analysis or a time-consuming and demanding lyophilization process, it was proposed to evaporate the water at room temperature under compressed air (Figure 1), without or after ultracentrifugation of the dispersion (Supplementary Material Figure S1). The thermal transformation peaks of the lipids obtained in both cases were very similar (Figure S1), although in the formulation subjected to centrifugation the peak had a slightly less regular shape, lower height and greater width. Considering the small mass of microspheres used for DSC analysis, it is enough to evaporate water from a small volume of dispersion. Bearing in mind the effect of centrifugal forces during centrifugation, which may also affect the properties of the microspheres, it was ultimately considered beneficial to abandon the centrifugation step. As the final and most advantageous solution, it is therefore proposed to use only the evaporation of water from SLM dispersion under compressed air at room temperature before analysis. When pure drug substances were tested, cyclosporine exhibits no thermal events at 115 \({}^{\circ}\)C, characteristic for a crystalline drug [23], because the endothermic peak is shifted to 128 \({}^{\circ}\)C (Figure 2). The peak observed at this temperature probably results from the solid-to-liquid transition of the drug substance at temperatures above 120 \({}^{\circ}\)C. The same phenomenon was observed by [PERSON] et al. [23] and [PERSON] et al. [13], when they studied the crystalline and amorphous form of CsA. Indomethacin, as a commercial bulk material, usually occurs in the most thermodynamically stable \(\gamma\) form, although it can also exist in the \(\alpha\) polymorphic form as well as in the amorphous solid form.