Ion pair formation and gastrointestinal absorption of emepronium.

Abstract

Ion pair forming agents were evaluated in vitro for their ability to form lipophilic ion pairs with the quaternary ammonium compound emepronium and in vivo to enhance its gastrointestinal absorption. A 5- to 100-fold excess of trichloroacetate (TCA), diethylhexylphosphate (DEHPA), heptafluorobutyrate (HFBA), sodium lauryl sulphate (SLS), bromide or chloride all increased the extractability of the emepronium ion into methylene chloride. The additive with the most marked effect on the apparent partition coefficient of emepronium (Kapp) was SLS. At emepronium 10(-4) M, Kapp increased from a basal value of 0.1 to 368 with a 100-fold molar excess. However, the increased partitioning to methylene chloride was not reflected in an increased gastrointestinal absorption of the emepronium ion when this was given orally to mice. When intestinal juice, instead of distilled water or buffer, was used as the aqueous phase, the partition coefficient was markedly higher (Kapp approximately 2) but it was significantly less influenced by addition of sodium lauryl sulphate (Kapp approximately 6). The preexisting positive influence of the intestinal juice on the lipophilic character of emepronium and the rather limited additive effect of agents that form lipophilic complexes with emepronium, lead to the conclusion that the ion pair concept is not a suitable approach to enhance the gastrointestinal absorption of this drug.