Prediction of percutaneous drug permeability using modified theoretical linear solvation energy relationship

Abstract

To predict the percutaneous drug permeability coefficients with modified regression equation. The semiempirical self-consistent field molecular orbital calculation AM1 method was used to calculate the quantum chemical parameters and the modified theoretical linear solvation energy relationship was used to obtain the regression equation of the permeability coefficients of drugs through human epidermis. The permeability coefficients (P) of 36 nonelectrolytes were well linearly correlated with their theoretical descriptors including molecular volume (V), hydrogen bond acidity (sum alpha(2)(H)), hydrogen bond basicity (sum beta(2)(H)) and polarizability index (pi(1)). The regression equation was logP=-6.790+1.571 V+0.1550 pi(1)-1.295 sum alpha(2)(H)-2.485 sum beta(2)(H)(n=36,r=0.9777). The modified theoretical linear solvation energy relationship can be used to predict the skin permeability of drugs.