Relationship between nasal absorption and physicochemical properties of quaternary ammonium compounds

The present study was undertaken to investigate the in situ nasal absorption of a series of tetraethylammonium chloride-related aliphatic quaternary ammonium compounds in rats and its relationship with their physicochemical properties (molecular weight and partition coefficient). All of the ten quaternary ammonium compounds examined were found to be absorbed through the nasal mucosa of rats. The nasal absorption rates of ethyltrimethyl-ammonium iodide and tetraethylammonium chloride, with the lowest molecular weight, were the highest, and those of tetra-n-butylammonium chloride and tetra-n-propylammonium bromide, with high molecular weight, were much lower. Thus, there was a tendency that the nasal absorption rates of quaternary ammonium compounds in rats decreased with an increase in their molecular weight. A physicochemical study has shown that there was a linear relationship between the molecular weight of the ten quaternary ammonium compounds and their partition coefficient, thereby suggesting an increase in lipophilicity with the molecular weight. In addition, there was a good correlation between the extent of the nasal absorption of the quaternary ammonium compounds studied and their molecular weight or partition coefficient. These data suggest that there is a reciprocal relationship between the membrane transport of quaternary ammonium compounds in the nasal mucosa and their lipophilic character. In conclusion, it seems likely that quaternary ammonium compounds are predominantly absorbed from the nasal mucosa of the rat through waterfilled channels or pores rather than through the lipid membrane.