• membrane transport;
  • lipid bilayers;
  • peptide permeability;
  • partition coefficients;
  • solubility-diffusion theory


The barrier domain solubility-diffusion theory of lipid bilayer permeability relates the permeability coefficient (Pm) to the solute's partition coefficient (PCbarrier/w) and diffusion coefficient (Dbarrier) in the ordered chain region of the bilayer that serves as the barrier region for polar permeants. To select the best solvent to mimic the barrier domain, permeability coefficients across a layer of 1,9-decadiene were compared with permeability coefficients from bilayer transport. Rate constants for transport, k, of α-methyl substituted analogues of p-toluic and p-methylhippuric acid were measured across a layer of 1,9-decadiene embedded in a PTFE filter membrane placed between two aqueous solutions in side-by-side diffusion cells. Permeability coefficients (P1,9-decadiene) were normalized to that obtained for p-toluic acid, which was included in donor solutions. The correlation of log(Pbilayer) versus log(P1,9-decadiene) was linear with a slope of 0.99 ± 0.02 SD, indicating that 1,9-decadiene precisely mimics the egg lecithin bilayer barrier domain in its chemical selectivity. Using the decadiene membrane transport method to indirectly estimate partition coefficients for similarly sized permeants extended the range of measurable values beyond those readily attainable by the traditional shake-flask method, allowing measurement of 1,9-decadiene/water PCs as low as 3 × 10−7. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:640–646, 2002