Lipophilicity behaviour of the zwitterionic antihistamine cetirizine in phosphatidylcholine liposomes/water systems

Purpose. The partitioning of cetirizine in a phosphatidylcholine liposomes/ water system was compared with that of hydroxyzine and acrivastine to gain insight into the mechanisms of interaction of its various electrical specie s with membranes. Methods. The lipophilicity profiles of the compounds were obtained from equ ilibrium dialysis and potentiometry, and compared with changes in NMR relax ation rates. Results. The neutral form of hydroxyzine interacted mainly via hydrophobic interactions with the bilayer lipid core of the membrane, whereas for the c ationic form both hydrophobic and electrostatic interactions were involved. Zwitterionic and anionic cetirizine were less lipophilic than its cation, which behaved like the corresponding species of hydroxyzine. Zwitterionic c etirizine interacted more by weak electrostatic interactions with the polar headgroups of phospholipids than by hydrophobic interactions with the memb rane interior. The lipophilicity of its anion reflected the balance of repu lsive electrostatic interactions between the carboxylate and phosphate grou ps and the hydrophobic interactions with the lipid core. Conclusion, The study confirms that various mechanisms influence the intera ction of solutes with liposomes. Combining experimental techniques and usin g suitable reference compounds proves useful.