Synthesis and topical delivery of N-alkyl-N-alkyloxycarbonylaminomethyl prodrugs of a model phenolic drug: Acetaminophen

The synthesis, physicochemical characterization and flux of a homologous series of N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of a model phenolic drug, acetaminophen (APAP), have been investigated. The most water soluble member of the series gave the highest transdermal delivery from isopropyl myristate (IPM) through hairless mouse skin. The flux of NANAOCAM prodrugs of APAP was accurately predicted by the Roberts–Sloan (RS) equation.