2.2.1. Thermoanalytical Studies

The thermoanalytical TG/DTG/HF curves of the RSP/RM-β-CD inclusion complex and its mixture with pharmaceutical excipients, recorded in dynamic air atmosphere and heating rate of 10 ◦C·min−<sup>1</sup> are presented in Figure 8a–c.

**Figure 8.** TG (**a**), DTG (**b**), and HF (**c**) curves of RSP/RM-β-CD inclusion complex (1) and its mixtures with excipients, as follows: RSP/RM-β-CD + STR (2); RSP/RM-β-CD + CEL (3); RSP/RM-β-CD + MgSTE (4); RSP/RM-β-CD + LCT (5).

The TG/DTG curves of RSP/RM-β-CD inclusion complex suggests its thermal degradation in the following temperature ranges: 35–86 ◦C (∆*m* = 5.2%, dehydration process), 197–338 ◦C (∆*m* = 32%, DTGpeak at 309 ◦C), 338–414 ◦C (∆*m* = 28.8%, DTGpeak at 351 ◦C) and 414–510 ◦C (∆*m* = 13.2%, DTGpeak at 490 ◦C). The HF curve of inclusion complex reveals two exothermic events, a small one at 313 ◦C and another one at 487 ◦C, corresponding to the decomposition of the complex.

Regarding the inclusion complex–excipients physical mixtures, in all situations, thermoanalytical TG/DTG curves show a mass loss process at temperatures lower than 110 ◦C due to the release of water from complex and/or excipient. For the mixtures with CEL and LCT, the dehydration occurs at temperatures below 100 ◦C, as follows: RSP/RM-β-CD + CEL has water loss up to 92 ◦C, with ∆*m* = 4.47% and RSP/RM-β-CD + LCT has water loss up to 68 ◦C, with ∆*m* = 1.71%. In the case of mixtures with STR and MgSTE, the dehydration takes place up to higher temperatures, as follows: RSP/RM-β-CD + STR reaches constant mass at 124 ◦C, after a mass loss ∆*m* = 7.98%, while for RSP/RM-β-CD + MgSTE, the dehydration is complete at 106 ◦C, with a corresponding ∆*m* = 4.31% (DTG process in 94–107 ◦C temperature range, DTGmax at 103 ◦C).

The stability profile of mixtures with excipients in an anhydrous state is good, as revealed by the thermoanalytical curves. Accordingly to this, the RSP/RM-β-CD + STR mixture shows no thermal events in the 124–214 ◦C, while with the increase of thermal stress, the decomposition begins. TG/DTG curves reveal a continuous mass loss process in the temperature range 214–510 ◦C (DTGmax at 292 ◦C), with a corresponding ∆*m* = 77.78%. The HF curve does not reveal significant events up to 289 ◦C, when some exothermal processes are observed, due to the oxidative thermolysis of organic edifice (HFmax at

301 ◦C, 338 ◦C and 457 ◦C, respectively). In the case of the RSP/RM-β-CD + CEL mixture, thermoanalytical data suggest that the anhydrous mixture is stable in the 92–232 ◦C temperature range, since none of the three thermoanalytical curves reveal any process. In the temperature range 232–510 ◦C, a consistent mass loss is observed (∆*m* = 91.37%), which is sustained by the DTG profile (main process between 233 and 391 ◦C, DTGmax at 322 ◦C, shoulder at 349 ◦C), secondary process between 391 and 510 ◦C, DTGmax at 459 ◦C). The HF curve reveals oxidative thermodegradation at temperatures over 233 ◦C, with HFmax at 264, 334, and 459 ◦C, respectively. The mixture RSP/RM-β-CD + MgSTE shows the most complex thermoanalytical profile, due to complexity of excipient composition, being known that pharmaceutical-purity MgSTE is a mix of different fatty acid salts that may vary in proportion, and additionally, its properties heavily depend on its moisture content [53,54]. After the dehydration, the RSP/RM-β-CD + MgSTE shows stability in the 106–218 ◦C temperature range, without revealing any interactions between the components of this matrix. The main mass loss process takes place in the 218–510 ◦C (∆*m* = 81.64%), with several DTG peaks at 321, 354, 422, 444, and 519 ◦C, respectively), and it is accompanied by several HF peaks corresponding to an endothermic event—dehydration (96–111 ◦C, HFpeak at 104 ◦C), and with the increase of temperature with exothermic ones, in the 303–510 ◦C range: 327, 356, 428, and 524 ◦C, respectively. Last, for the RSP/RM-β-CD + LCT sample, the stability in anhydrous state is observed in the range 68–110 ◦C; then, a small mass loss takes place in the range 110–143 ◦C (∆*m* = 1.65%), which is followed by the main mass loss process that takes place in the range 196–510 ◦C (∆*m* = 66.18%). The DTG profile is more complex in this case, revealing peaks up to 210 ◦C at 63, 117, and 133 ◦C), and in the temperature range 200–510 ◦C at 238 (main), 272, 283, 322, and 482 ◦C, respectively). The HF curve reveals some endothermal events at 119 ◦C and 221 ◦C, while the thermal events associated with the thermooxidation of complex are no longer visible at temperatures over 300 ◦C. This behavior is a clear indication that some incompatibilities take place in this system, which are mainly due to the fact that they are facilitated by the presence of the melted excipient (LCT), which occurs in the range 203–243 ◦C (HFpeak at 221 ◦C). The stability profile of mixtures with excipients in an anhydrous state is good, as revealed by the thermoanalytical curves, and no interactions are revealed between the inclusion complex and three of the selected excipients (STR, CEL, and MgSTE), while for mixture with LCT, interactions are observed during the thermal treatment of the samples. For this last sample, a concrete evaluation of interactions can be realized solely by the implementation of two other investigational tools, namely UATR-FTIR and PXRD.
