Synthesis and comparative skin permeability of atenolol and propranolol esters

The prodrug approach is one of the methods which have been evaluated for improving the systemic delivery of pharmacologically active compounds. In the present study, we have synthesized ester prodrugs of atenolol and propranolol by adding alkyl side chains to the beta-hydroxy function of the drug with the objective of enhancing their lipophilicity. In vitro skin permeability study in excised mice skin showed that the prodrugs permeate freely through the skin than the respective drug moieties and significant flux enhancement (6.2-fold) was observed in both cases. In the case of atenolol, the highest permeability coefficient was shown by capriate (C-10 side chain) where as in propranolol the highest permeability was recorded with caproate ester (C-6 side chain). The difference in permeability may be attributed to their difference in the intrinsic lipophilicities.