## 3 Results and Discussion
### In Vitro Drug Release Analysis  
The drug-loading percentage of BUD in the interior cavity of CD is a significant parameter directly affecting the release profile with a major impact on the systemic absorption inducing higher bioavailability [36]. In the present study, the effect of different solvent ratios was examined. Table 3 summarizes the drug-loading efficiency in the CD-BUD-10% for H\({}_{2}\)O/EtOH ratios varying from 50/50 to 90/10. It is evident that, by diminishing the amount of the organic solvent from 50/50 to 80/20 ratio, the drug loading increases. The organic solvent competes with the hydrophobic BUD molecules to enter the hydrophobic CD cavity. Consequently, with a lower ratio of EtOH, BUD can be more easily entrapped in  
Figure 11: TGA curves of BUD, CD and CD–BUD 5%, CD–BUD 10%, CD–BUD 20% and CD–BUD 30%. Figure 10: DSC curves of (**a**) BUD and (**b**) CD–BUD 5%, CD–BUD 10%, CD–BUD 20% and CD–BUD 30%. CD complexes. However, in the ratio 90/10, the drug-loading percentage decreases, which is attributed to the inability of BUD to be completely dissolved under these conditions, forming inclusion complexes with a lower drug loading percentage. In a further step, the dissolution profile of the inclusion complexes was conducted (Figure 12). The in vitro release profile of BUD from the CD-BUD complexes is highly associated with the degree of crystallinity of the samples. Active compounds entrapped in the amorphous phase are estimated to have an enhanced dissolution profile since the amorphous state of the drugs is characterized by a disordered structure in comparison to the crystalline state with higher free energy [37]. BUD as a crystalline, hydrophobic compound presents an in vitro dissolution ability of up to 13%. The inclusion of BUD in CD complexes leads to the amelioration of the active compound's release behavior. As expected, the optimum release behavior was measured in the sample with H2O/EtOH ratio 80/20, releasing up to 65% of the embedded drug. The samples with higher degrees of crystallinity presented inferior in vitro release. However, all the inclusion complexes presented a two-phase release profile. An initial burst release during the first 7 h which is followed by a sustain release up to 10 days. At a subsequent level, the drug loading percentage of BUD in the samples CD-BUD 5 wt%, 10 wt%, 20 wt%, and 30 wt% was estimated. Table 4 presents the increasing loading percentage, as the amount of BUD added in the inclusion complexes increases. Since the ratio of the organic solvent is constant (80/20 _v/v_), the loading percentage is affected solely by the presence of BUD. The results are in agreement with the literature, since the incorporation of a lipophilic drug into inclusion complexes results in the improvement of its loading efficacy [38; 39]. Figure 12: In vitro release of BUD from CD inclusion complexes at pH 7.4. In vitro release was estimated in the samples CD-BUD 5 wt%, 10 wt%, 20 wt%, and 30 wt%. Their release profiles are similar to the in vitro release of the samples CD-BUD-10 with various H\({}_{2}\)O/EtOH ratios with a two-phase dissolution profile, an initial burst release, followed by a sustain release (Figure 13). Interesting is the fact that a higher release is achieved by the sample with a lower amount of BUD, CD-BUD-5% equal to 78.7%. This release behavior is characteristic for lipophilic drugs owed to hydrophobic interactions taking place between the drugs' molecules. According to literature data, the entrapment of hydrophobic active substances in polymeric matrices results in an inversely proportional relationship between drug concentration and drug release. When the drug amount becomes higher, the drug release is reduced [40; 41; 42]. Furthermore, as the percentage of BUD increases, the percentage of the released drug is diminished. The maximum dissolution percentage of the samples CD-BUD 10 wt%, 20 wt%, and 30 wt% are 61.8%, 51.5%, and 27.2% respectively. Moreover, the release profiles are according to the degree of crystallinity of the samples.