Study of the inclusion complexes formed between cetirizine and α‐, β‐, and γ‐cyclodextrin and evaluation on their taste‐masking properties

Complexation properties of cetirizine dihydrochloride (cetirizine) with α‐, β‐, and γ‐cyclodextrin (CD) were investigated by ultra violet (UV) and nuclear magnetic resonance (NMR) spectroscopies and isothermal titration calorimetry (ITC). The use of the continuous variation method, applied on UV and nmR data, demonstrated 1:1 complex stoichiometry for cetirizine-α‐CD, cetirizine-β‐CD, and cetirizine-γ‐CD, respectively. nmR two‐dimensional Rotational nuclear Overhauser Effect SpectroscopY experiments revealed that for α‐ and β‐CD, the complexation takes place by including either the phenyl or chlorophenyl ring of the cetirizine into the CD cavity, whereas in the case of γ‐CD, both rings can be included simultaneously. Association constants (Ka) determined by UV spectroscopy demonstrated that cetirizine forms more stable complex with β‐CD (Ka = 5641 ± 358 M−1) than α‐CD (Ka = 1434 ± 60 M−1). No information could be extracted from the UV spectroscopic analysis of cetirizine-γ‐CD solutions. ITC results for association constant determination were in compliance with UV results and confirmed that the highest association constant was found for the cetirizine-β‐CD complex (2540 ± 122 M−1). The association constants from ITC measurements for cetirizine-γ‐CD and cetirizine-α‐CD complexes were found to be 1200 ± 50 and 800 ± 22 M−1, respectively. Taste‐masking studies revealed that β‐CD is the only native CD recommendable for oral pharmaceutical formulations. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3177-3185, 2011