Thermodynamic Study of Partitioning and Solvation of (+)-Naproxen in Some Organic Solvent/Buffer and Liposome Systems

Abstract

Naproxen (NAP) partitioning thermodynamics was studied in different solvent/buffer systems such as cyclohexane (CH/W), octanol (ROH/W), isopropyl myristate (IPM/W), and chloroform (CLF/W), as well as in dimyristoyl phosphatidylcholine (DMPC) and dipalmitoyl phosphatidylcholine (DPPC) liposome systems. In all cases, the mole fraction partition coefficients (K X o/w ) were greater than unity; therefore, the standard Gibbs energies of transfer were negative indicating a high affinity of NAP for all the organic media. K X o/w values were approximately 1000-fold higher in the ROH/W system with respect to the CH/W system, thus indicating a high degree of hydrogen-bonding contribution to partitioning, whereas in the case of the IPM/W and CLF/W systems, the K X o/w values were approximately only 2-fold or 5-fold lower than those observed in ROH/W. On the other hand, K X o/w values were approximately 55-fold or 39-fold higher in the liposomes compared to the ROH/W system, for DMPC and DPPC, respectively, thus indicating a high degree of bilayer immobilization and/or an electrostatic contribution to partitioning. In almost all cases, standard enthalpies of transfer of NAP from water to organic solvents were negative (except for CH), whereas the standard entropies of transfer were positive (except for IPM). For liposomes, the standard enthalpies and entropies of transfer were positive. These results indicate some degree of participation of the hydrophobic hydration on the NAP partitioning processes. By using the reported data for solvation of NAP in water, the associated thermodynamic functions for NAP solvation in all tested organic phases were also calculated. Finally, all the results obtained for NAP were compared with those presented previously for ketoprofen.