A novel device for the determination of liposome/water partition coefficients

Abstract

A novel, cheap and easy-to-construct device and a simple method for partition coefficient determination in liposome/water system based on modified equilibrium dialysis have been developed. The device consists of two vials separated by a semi-permeable membrane, through which the free form of a low molecular weight substance is transported by shaking assisted diffusion. Five test substances, eugenol, carvacrol, thymol, 4-hydroxybenzyl alcohol (4-HBA) and butylparaben were analyzed after equilibration in aqueous phase by three methods, HPLC-UV, GC-MS and DPV with comparable results. This shows the possibility of using the proposed method in any laboratory with any equipment capable of analyzing the substance under study. The liposome/water partition coefficients (log Pl/w) determined for eugenol (2.39), thymol (2.83), carvacrol (2.78) and butylparaben (3.30) are consistent with previously published data. A strong effect of NaCl on the liposome/water partition coefficient was observed. The value of log Pl/w = 1.06 determined for 4-HBA in the presence of 0.15 mol L-1 NaCl in the partitioning liposomal system was considerably lower than in the absence of the salt (log Pl/w = 2.06). The developed method was used to determine the partition coefficient of morphine in liposome/water system without NaCl (log Pl/w = 2.65) under given conditions.