Distribution of Prostaglandin E₁ in Lipid Emulsion in Relation to Release Rate from Lipid Particles

Abstract

The distribution style of prostaglandin E₁ (PGE₁) in injectable lipid emulsion (Lipo-PGE₁) was analyzed using a three-phase model : an aqueous phase, an oil phase and an oil/water interface. A combination of the oil phase and the oil/water interface was obtained as the particle phase. Initial diffusion rates of PGE₁ from lipid particls to the aqueous phase were determined by the dialysis method, and equilibrium concentrations were calculated by the diffusion rates using an equation derived from Fick's theory. Lipo-PGE₁ enclosed in cellulose tubing was immersed in buffer solutions (pH 5.5, 7.4), then incubated at various constant temperatures. Each concentration of PGE₁ in the aqueous phase was measured at appropriate intervals. By using these values, partition coefficients between the particle phase and the aqueous phase were calculated. It was found that a larger portion of PGE₁ was distributed in the particle phase compared with the aqueous phase in Lipo-PGE₁ at each temperature. Furthermore, actural partition coefficients between oil and aqueous phases were measured. From the results of two partition coefficients, the distribution ratio of PGE₁ in Lipo-PGE₁ was determined as : oil : oil/water interface : water=0.2 : 93.1 : 6.7, that is, 93% PGE₁ was found to be distributed in lipid particles. On the other hand, by diluting PGE₁ one hundred times with transfusion, the distribution ratio of PGE₁ in lipid particles decreased as the pH of the transfusion increased. The ratios after 2 h were 74% and 47% for pH 5.5 and 7.4, respectively.In conclusion, a large portion of PGE₁ was found to be distributed in the particle phase when Lipo-PGE₁ was diluted with transfusion. Since most PGE₁ exists in an oil/water interface, it is considered that it has a strong affinity for phospholipids. Thus, this affinity may contribute to the remarkable increase in activity in clinical treatment.