Corneal penetration behavior of beta-blocking agents I: Physiochemical factors

Abstract

Rabbit corneas were excised and mounted in a chamber to determine the permeability characteristics of a group of beta-blocking agents which varied in octanol-water partitioning over a fourfold logarithmic range. From the permeability rate at steady state, permeability coefficients (pH 7.65) were determined. For each drug the distribution coefficient and pKa were measured, permitting the partition coefficients to be estimated. Various correlations were determined for the log permeability coefficient as a sum of log functions of the partition (or distribution) coefficient, molecular weight, and/or degree of ionization. The best fit, as judged by a high correlation coefficient (r = 0.9756) and lack of systematic deviation, was represented by: log PT = 0.623 log DC - 0.108(log DC)2 - 5.0268.