Correlation of partition coefficients in n-heptane-aqueous systems with buccal absorption data for a series of amines and acids

Abstract

Partition coefficients in n-heptane-0·1n sodium hydroxide or 0·1n hydrochloric acid have been determined for a series of amines and acids; linear relations between chain-lengths and the logs of their partition coefficients were found. The plot of alkyl chain-length against buccal absorption of some amphetamines and fenfluramines, when they were 1% unionized, was linear. There was also a linear relation between the logs of the partition coefficients and buccal absorption of the amines and acids when these were 1 and 10% unionized. Those amines and acids having similar partition coefficients, when equally unionized, were absorbed to the same extent in the buccal test over the pH range 4 to 9. During the test the pH at the surface of the buccal membrane was shown to be the same as that of the solution in the mouth. n-Heptane is considered to be equivalent in solvent properties to the buccal lipid membrane for the compounds used in the present test.