**4. Conclusions**

The complex formation between different sulfonamides and cyclodextrins still has attract much attention. Previous studies described the ability of cyclodextrin to increase the solubility of these drugs in water [23,24]. Subsequently, efforts were made to study the structure of the complexes by experimental and molecular modelling techniques [18,23,24]. Earlier studies focus on the buffer free solution, suspension or freeze-dried solid state complexes. According to our present knowledge our work is the first study to describe the sulfamethazine–β-cyclodextrin and sulfamethazine–randomly methylated β-cyclodextrin complexes in aqueous solution at different pH and temperature values using combined experimental and theoretical techniques. Both spectroscopic measurements and molecular modeling studies highlight the importance of the reorganization of the solvent molecules during the guest molecule enters the host's cavity. Results highlight formation of zwitterionic sulfamethazine molecule in the cyclodextrin cavity which affect significantly the stability of SMT-CD complexes. The pH-affected structures of the complexes investigated explain the previous contradictory findings. The presented results might relevant for the preparation of orally administreted products of sulfamethazine-cyclodextrin complexes.

**Author Contributions:** Conceptualization, B.L. and S.K.-M.; methodology, B.L. and S.K.-M.; formal analysis, H.M.A.; investigation, H.M.A.; L.S.; M.P.; B.L. B.B. and S.K.-M.; resources, S.K.-M. L.S.; data curation, H.M.A.; B.L. and S.K.-M.; writing—original draft preparation, H.M.A.; L.S.; M.P.; B.L. and S.K.-M.; writing—review and editing B.L. and S.K.-M.

**Funding:** This research received no external funding.

**Acknowledgments:** This work was supported by the GINOP-2.3.2-15-2016-00049 grant.

**Conflicts of Interest:** The authors declare no conflict of interest.
