The influence of physico-chemical properties of homologous nicotinic acid esters on the permeability and maximum flux through an octanol membrane

Abstract

In a Schulman-type three compartment model with water as donor phase A and acceptor phase B and octanol as the lipophilic phase between them, rate constants of transfer from A to B, k AB, have been experimentally determined for homologous nicotinic acid esters (methyl nicotinate, MN, ethyl nicotinate, EN, butyl nicotinate, BN, hexyl nicotinate, HN, and octyl nicotinate, ON). The k AB-values are rather independent of the partition coefficient octanol/water PC oct/W of the respective esters, demonstrating diffusion control in aqueous boundary layers. Thus, the calculated permeabilities of the homologous esters for a three layer membrane water/octanol/water also show values of similar magnitude. The logarithms of the maximum fluxes J max of the esters through this three layer membrane exhibit an inverse proportionality to the number of C-atoms in the alkyl chain. The slope of the respective straight line corresponds well with the incremental constant δ for the relationship between the logarithms of the water solubilities and the alkyl chain length. This confirms the distinctive influence of aqueous boundary layers on the drug transfer through octanol membranes in vitro.