The distribution and chemical kinetics of prostaglandin E 1 in lipid emulsions

Abstract

The partitioning of PGE 1 in a lipid emulsion has been shown to be consistent with a three-phase model which assumes that solute may reside in the bulk aqueous and oil phases and at the oil-water interface. Ultrafiltration and dialysis techniques were used to estimate the relative percentages of PGE 1 in each phase at various pHs. The amount of PGE 1 present in the bulk oil phase of the emulsion was concluded to be insignificant. At emulsion pH values of less than five, PGE 1 resides preferentially at the interface. With increasing pH, the percentage of PGE 1 in the aqueous phase increases. A model which assumes that both the non-ionized and ionized PGE 1 species may be present at the interface, depending on pH, was shown to be consistent with the data. Estimates were made of the distribution coefficients of the ionized and non-ionized PGE 1 between the interface and the aqueous phase and their concentration dependence. The distribution coefficients were used to generate a distribution profile of the various PGE 1 species as a function of pH. The overall dehydration kinetics of PGE 1 in a lipid emulsion were found to fit a model whereby the k apparent measured at each pH is simply the sum of the product of the fraction of the PGE 1 at the interface, f i , and the rate constant at the interface, k i, plus the product of the fraction of the PGE 1 in the aqueous phase, f aq , and the rate constant in the aqueous phase, k aq. The k aq and k apparent were experimentally determined as a function of pH. The k i was indirectly determined from the stability data in the emulsion. Microscopic rate constants for dehydration of PGE 1 in the aqueous phase and interface were estimated from the experimental data. The dehydration kinetics were also shown to be affected by the addition of charged surface active agents.