Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486335 | Journal of Pharmaceutical Sciences | 2011 | 9 Pages |
Abstract
Complexation properties of cetirizine dihydrochloride (cetirizine) with αâ, βâ, and γâcyclodextrin (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-αâCD, cetirizine-βâCD, and cetirizine-γâCD, respectively. nmR twoâdimensional Rotational nuclear Overhauser Effect SpectroscopY experiments revealed that for αâ and βâCD, the complexation takes place by including either the phenyl or chlorophenyl ring of the cetirizine into the CD cavity, whereas in the case of γâCD, both rings can be included simultaneously. Association constants (Ka) determined by UV spectroscopy demonstrated that cetirizine forms more stable complex with βâCD (Ka = 5641 ± 358 Mâ1) than αâCD (Ka = 1434 ± 60 Mâ1). No information could be extracted from the UV spectroscopic analysis of cetirizine-γâCD 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-βâCD complex (2540 ± 122 Mâ1). The association constants from ITC measurements for cetirizine-γâCD and cetirizine-αâCD complexes were found to be 1200 ± 50 and 800 ± 22 Mâ1, respectively. Tasteâmasking studies revealed that βâCD is the only native CD recommendable for oral pharmaceutical formulations. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:3177-3185, 2011
Keywords
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Authors
Mladen Stojanov, Reinhard Wimmer, Kim L. Larsen,