Mechanism of Indomethacin Partition between n-Octanol and Water

Abstract

To examine the fundamental process of the transfer of indomethacin (LND) to the biological membrane, the partition coefficient between n-octanol and water was measured at various pH values or in the presence of various cations by the shaking-flask method at 25°C. The apparent partition coefficient decreased with increase in pH and the true partition coefficient of unionized IND was determined to be 1.20×10⁴, while that of ionized IND was 1.72×10^-1. The IND anion was found to be readily transferred to the hydrophobic region by forming ion-pair complexes with cations in the aqueous phase. The ion-pair complex of IND with the ammonium ion was transferred to the organic phase more readily than that with the sodium or potassiumion. In this study, a method for quantitative analysis of the ion-pair partition of an unstable drug at alkaline pH was established under conditions where more than two cationic species were present.