Determination of the pH-dependent phase distribution of prostaglandin E1 in a lipid emulsion by ultrafiltration.
The distribution of prostaglandin E1 (PGE1) 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. Calculations suggest that, in a lipid emulsion having an average particle size of 0.11 micron, it is theoretically possible for a surface active species such as PGE1 to exist predominantly at the interface. Aqueous phase concentrations of PGE1 versus pH were measured in an emulsion having an oil/water phase volume ratio of 0.1 by the use of an ultrafiltration technique in order to estimate the relative percentages of PGE1 in each phase. From bulk oil/water partition coefficient determinations, the amount of PGE1 present in the bulk oil phase of the emulsion was concluded to be insignificant. At emulsion pH values less than 5, PGE1 resides preferentially (greater than 97%) at the interface. With increasing pH's, the percentage of PGE1 in the aqueous phase increases, reaching 51% at high pH's. A model which assumes that both the nonionized and the ionized PGE1 species may be present at the interface, depending on the pH, was shown to be consistent with the data. Estimates were made of the distribution coefficients of the ionized and nonionized PGE1 between the interface and the aqueous phase and their concentration dependence. The apparent pKa of PGE1 at the interface derived from these data was 6.8. The distribution coefficients were used to generate a distribution profile of the various PGE1 species as a function of the pH. This distribution profile will be useful in explaining kinetic data of PGE1 in the emulsion as a function of pH.
Teagarden
D L
DL
Pharmaceutical Manufacturing Technical Support, Upjohn Company, Kalamazo, Michigan 49001.
Anderson
B D
BD
Petre
W J
WJ
D000527:Alprostadil / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions; D006863:Hydrogen-Ion Concentration; D010316:Particle Size; D014462:Ultrafiltration
D004655:Emulsions; D000527:Alprostadil