## 3 Results and Discussion  
### The Effect of Solvent Ratio in Budesonide Cyclodextrin Inclusion Complexes  
The formation of inclusion complexes between CD and various hydrophobic compounds has been examined extensively since it aids in the development of stable formulations with enhanced bioavailability [20]. During the formation of the complexes, it is significant to estimate how the effective inclusion affects the properties of drugs when CD complexes are formulated [21]. Figure 2 depicts the phase-solubility diagram of BUD with CD. According to [PERSON] and [PERSON], the obtained curve is characterized as an \"A type\" phase-solubility profile, describing the increase of BUD solubility as the CD concentration increases. The A-type models indicate that one drug molecule forms a complex with one molecule of CD and a linear relationship exhibits [22]. Beta-CD is the least water soluble among the cyclodext and BUD is a water-insoluble active compound. Consequently, their further effective complexation would take place in the presence of an organic solvent. The applied solvent ratio is of crucial importance since the organic solvent, in this work ethanol, competes with drug molecules for their successful inclusion in the hydrophobic cavity of CD [23]. In the present study, the utilized solvent system is H\({}_{2}\)O/EtOH. The amount of the organic solvent affects the inclusion efficacy of the hydrophobic compound, i.e., BUD in the interior cavity of CD as well as the crystallinity of the final samples, thereafter [14]. Consequently, different H\({}_{2}\)O/EtOH ratios (50/50, 60/40, 70/30, 80/20, and 90/10 \(v\)/\(v\)) were examined for obtaining the optimum inclusion efficacy, with the minimum amount of crystallinity. For this purpose, the inclusion of BUD in the CD cavity in a 10%wt ratio was conducted. Figure 3 depicts the FTIR spectra of CD-BUD samples for the various H\({}_{2}\)O/EtOH ratios. The spectra on neat CD showed the characteristic peaks of the oligosaccharideschardie present at 3400 cm\({}^{-1}\) attributed to O-H stretching vibration, at 2930 cm\({}^{-1}\) to the C-H stretching vibration, at 1640 cm\({}^{-1}\) the O-H bending vibration, at 1155 cm\({}^{-1}\) the C-H vibration and at 1029 cm\({}^{-1}\) the C-O vibration [24]. BUD characteristic peaks are present at 3499 cm\({}^{-1}\) region of the O-H stretching vibration, at 2955 cm\({}^{-1}\) methyl groups stretching vibration (C-H), at 1722 cm\({}^{-1}\) and 1670 cm\({}^{-1}\) stretching vibration of carbonyl groups (C=O) and at 1626 cm\({}^{-1}\) stretching vibration of the double bond (C=C) [25]. Comparing the spectra of neat CD, with the inclusion complexes, characteristic peaks attributed to the presence of BUD appear (Figure 3). More specifically, the peaks present at 2956 cm\({}^{-1}\), 1720 cm\({}^{-1}\) and 1670 cm\({}^{-1}\) are attributed to BUD. The peaks are slightly shifted in comparison to the neat drug, owing to interactions among the oligosaccharide and BUD. In a further step, the successful complexation was confirmed through \({}^{1}\)H-NMR measurements. In Figure 4, the H-3 and H-5 are the protons which are found inside the cavity of  
Figure 3: FTIR spectra of BUD, CD and CD–BUD inclusion complexes containing 10 wt% BUD after treatment at different H\({}_{2}\)O/EtOH ratios (50/50, 60/40, 70/30, 80/20 and 90/10 \(v\)/\(v\)). Figure 2: Phase-solubility diagram of BUD with CD, at 30 \({}^{\circ}\)C.  
CD and are the ones that are generally affected by complexation. In the \({}^{1}\)H-NMR spectrum of the CD-BUD complex, a slight upfield shift of the H-3 and H-5 protons is observed. This shift confirms the successful complexation of BUD in the CD cavity. SEM images were used for the examination of the inclusion complexes' morphology. According to the literature, CD presents an irregular block structure [26]. As depicted in Figure 5, in any solvent ratio, the obtained complexes were of irregular, spherical shaped, agglomerated particles. This observation is in accordance to the work of [PERSON] et al.