An investigation into the influence of binary drug solutions upon diffusion and partition processes in model membranes

Abstract

Few studies have assessed the impact of binary systems on the fundamental mathematical models that describe drug permeation. The aim of this work was to determine the influence of varying the proportions of prilocaine and lidocaine in a binary saturated solution on mass transfer across synthetic membranes. Infinite-dose permeation studies were performed using Franz diffusion cells with either regenerated cellulose or silicone membranes, and partition coefficients were determined by drug loss over 24 h. There was a linear relationship between the flux of prilocaine and lidocaine through regenerated cellulose membrane (R(2) >or= 0.985, n = 5) and their normalised ratio in solution. This linear model was also applicable for the permeation of prilocaine through silicone membrane (R(2) = 0.991, n = 5), as its partition coefficient was independent of the drug ratio (15.84 +/- 1.41). However, the partition coefficient of lidocaine increased from 27.22 +/- 1.68 to 47.03 +/- 3.32 as the ratio of prilocaine increased and this resulted in a non-linear relationship between permeation and drug ratio. Irrespective of the membrane used, the permeation of one drug from a binary system was hindered by the presence of the second, which could be attributed to a reduction in available membrane diffusion volume.