Influences of 1-Dodecylazacycloheptan-2-one on Permeation of Membranes by Weak Electrolytes. 1. Theoretical Analysis of Weak Electrolyte Diffusion through Membranes and Studies Involving Silicone Rubber Membranes

Abstract

The pH dependency of permeation of weak electrolytes allows inferences to be made about the barrier characteristics of membranes. The influences of enhancers on pH–permeation profiles promise further mechanistic enlightenment. To explore issues of weak electrolyte mass transfer, a steady-state mathematical model for a hydrophobic membrane with aqueous pores existing in series with aqueous phases, presently a popular depiction of the skin and other biological barriers, has been developed. The case in which there are no pores is then considered theoretically and in studies involving the mass transfer of benzoic acid across silicone rubber membranes. Specifically, the flux of [14C]benzoic acid across Silastic sheeting as a function of pH was investigated. This isotropic membrane's behavior conformed to expectations drawn from the model in that the un-ionized species penetrated in proportion to benzoic acid's prevailing state of ionization, the membrane being all but impenetrable to the benzoate anion. The enhancer, 1-dodecylazacyclo-heptan-2-one (Azone), was then applied to the membrane in emulsions of increasing concentration. There were two important consequences of such application. First, the un-ionized species of benzoic acid partitioned into the emulsion droplets, lowering the activity of the permeant in the emulsion's continuous phase. Second, Azone was imbibed to a degree into the polymeric membrane, significantly altering the permeability of the silicone rubber of which it is composed. The former influence had to be carefully factored out in order to delineate Azone's intrinsic enhancing effects on the membrane. The silicone rubber membrane system served well as a model for study of the enhancing effects of Azone on a wholly hydrophobic barrier, establishing a basis for the analysis of the actions of enhancers such as Azone on more complex, multiphasic biological barriers.