pH–metric log P. 6. Effects of sodium, potassium, and N‐CH3‐D‐glucamine on the Octanol–Water partitioning of prostaglandins E1 and E2

Alex Avdeef, Karl J. Box, Krisztina Takács‐Novák

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26 Citations (Scopus)

Abstract

The pH‐dependent octanol–water partition behavior of prostaglandins (Pg) E1 and E2 was studied by an automated potentiometric titration method. In 0.15 M KCl at 25 °C, the log P values of PgE1 and PgE2 are 3.20 ± 0.02 and 2.90 ± 0.02, respectively. The partition parameter also was determined in 0.15 M NaCl, 0.10 M NaCl, and 0.0003 M KCl for PgE1; no ionic strength dependence was observed. In contrast, the Pg anion partitioning, described by the extraction constant, log Ke (= [XPg]OCT/[X]AQ[Pg]AQ, where X = Na or K), showed dependence on the nature and concentration of the background salt. For PgE1, the log Ke values are 0.50 ± 0.08 (0.15 M KCl), 0.18 ± 0.16 (0.15 M NaCl), 0.86 ± 0.08 (0.10 M NaCl), and 1.80 ± 0.09 (0.0003 M KCl); for PgE2, the log Ke value is 0.20 ± 0.29. The extraction of the Pg anion into octanol by N‐methyl‐D‐glucamine (glucamine) was also studied. In 0.15 M KCl, the log Ke value is 1.82 ± 0.07. The extraction of the prostaglandin–glucamine complex into octanol maximizes at about pH 8.8. Due to the low aqueous solubility of the prostaglandins, the aqueous pKa values were determined by extrapolation from methanol–water solutions by the Yasuda–Shedlovsky technique. The Debye–Hückel theory was applied to predict the ionic strength dependence of the octanol–water ion‐pair extraction constants (log Ke).

Original languageEnglish
Pages (from-to)523-529
Number of pages7
JournalJournal of pharmaceutical sciences
Volume84
Issue number5
DOIs
Publication statusPublished - May 1995

ASJC Scopus subject areas

  • Pharmaceutical Science

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