A. Avdeef et al., PH-METRIC LOG-P .6. EFFECTS OF SODIUM, POTASSIUM, AND N-CH3-D-GLUCAMINE ON THE OCTANOL WATER PARTITIONING OF PROSTAGLANDINS E(1) AND E(2), Journal of pharmaceutical sciences, 84(5), 1995, pp. 523-529
The pH-dependent octanol-water partition behavior of prostaglandins (P
g) E(1) and E(2) was studied by an automated potentiometric titration
method. In 0.15 M KCl at 25 degrees C, the log P values of PgE(1) and
PgE(2) are 3.20 +/- 0.02 and 2.90 +/- 0.02, respectively. The partitio
n parameter also was determined in 0.15 M NaCl, 0.10 M NaCl, and 0.000
3 M KCl for PgE(1); no ionic strength dependence was observed. In cont
rast, the Pg anion partitioning, described by the extraction constant,
log K-e (=[X(+)Pg(-)](OCT)/[X(+)](AQ)[Pg(-)](AQ) where X = Na or K),
showed dependence on the nature and concentration of the background sa
lt. For PgE(1), the log K-e values are 0.50 +/- 0.08 (0.15 M KCl), 0.1
8 +/- 0.16 (0.15 M NaCl), 0.86 +/- 0.08 (0.10 M NaCl), and 1.80 +/- 0.
09 (0.0003 M KCl); for PgE(2), the log K-e value is 0.20 +/- 0.29. The
extraction of the Pg anion into octanol by N-methyl-D-glucamine (gluc
amine) was also studied. In 0.15 M KCl, the log K-e value is 1.82 +/-
0.07. The extraction of the prostaglandin-glucamine complex into octan
ol maximizes at about pH 8.8. Due to the low aqueous solubility of the
prostaglandins, the aqueous pK(a) values were determined by extrapola
tion from methanol-water solutions by the Yasuda-Shedlovsky technique.
The Debye-Huckel theory was applied to predict the ionic strength dep
endence of the octanol-water ion-pair extraction constants (log K-e).