Complexation of Citalopram with β-Cyclodextrin, Mono-subetadex, and Subetadex: Phase Solubility, Hummel–Dreyer, Affinity Capillary Electrophoresis, ITC, and NMR Studies

Cyclodextrins (CDs) have a number of important properties, such as chiral separation or the enhancing of water solubility of various substances. In the present study the complexation properties of sugammadex analog CDs, such as subetadex (SBX) and mono-subetadex (monoSBX) were investigated and compared with the native β-CD. The complexation features were investigated at pH 7.4 using citalopram, a selective serotonin reuptake inhibitor antidepressant, as a model compound. The stability constants were investigated by phase-solubility test, the Hummel-Dreyer (HD) method, affinity capillary electrophoresis, and ITC and the different analytical techniques were comprehensively evaluated and compared. The NMR studies supported the results from the investigated techniques and the complex structure was characterized by ROESY NMR studies. The phase-solubility study yielded results that deviated from the other three techniques, with monoSBX showing the highest stability constant. In the case of the HD method, the value of stability constants significantly differed from ACE and ITC, but the trend of CD stability followed the same order (β-CD < monoSBX < SBX). The ACE and ITC methods gave very similar results for β-CD and monoSBX, with some deviations for SBX, although still within the same order of magnitude. Based on the results ACE and ITC appear to be the most reliable techniques for determining CD-guest stability constants.