Interaction of Large Scale Organic Ions of Pharmaceutical Interest

Abstract

INTERACTION OF LARGE ORGANIC IONS OF PHARMACEUTICAL INTEREST Aqueous solutions containing large organic ions of opposite charge can provide useful information on ion pair formation in water and phase separation phenomena. The derived physicochemical parameters can find useful application in studies on formulation, drug transport mechanisms and hydrophobic interactions. The effect of molecular structure on thermodynamic parameters derived from the solubility product (Ks) for the 1:1 interaction between alkyl sulphates of differing chain lengths and substituted phosphonium compounds has been studied. Complexation has been followed using an automatic conductimetric titration apparatus. For a given cation, the solubility product changes logarithmically with the chain length of the alkyl sulphate. The change in free energy for the transfer of CH2 group from water to the separated phase is -3.14 kJ mol-1. It is larger than that found for the CH2 contribution in micelle formation of anionic surface active agents (-1.72 KJ mol-1) , but smaller than the value for transfer of the CH2 group from water to non-polar organic phase (-3.56 kJ mol-1) From considerations of entropy factors it is possible to conclude that the separated phase is a coacervate. The solubility product increases with ionic strength and with added urea (a material that destabilizes hydrophobic interactions). The change of Ks with temperature is similar to that found for the critical micelle concentration of alkyl sulphates and passes through a minimum. The contribution of the CH2 group to log Ks of 0.55 is similar to that obtained with the partition system 1-octanol-water used extensively by Hansch and co-workers in their π-o-p-analysis of structure-activity relations of drugs. The effects of aromatic substituents (OMe, OEt, NO2, Cl, Br, CN, cH3) on Ks have also been examined and it is suggested that the solubility product for 1:1 interaction between large ions may provide a simple but accurate method of obtaining π substituent constants.