The influence of alkyl substitution in acids on their performance in the buccal absorption test

A method to determine the passage of acids into the buccal membrane of man is presented. The absorption is shown to be the passive entry into a lipid phase. There is an increase in absorption of the acids due to alterations in partition characteristics with increasing chain length of n-fatty acids from butyric to dodecanoic. Methyl substitution of benzoic acid increases the absorption with mono- and di-substituents, but decreases the absorption with the tri- and tetra-substituents by lowering the pKa. Predictions of the relative absorption and excretion in man of these acids is included.