title: Synthesis and topical delivery of N-alkyl-N-alkyloxycarbonylaminomethyl prodrugs of a model phenolic drug: acetaminophen.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Susruta
authors.initials: S
authors.lastname: Majumdar
authors.forename: K B
authors.initials: KB
authors.lastname: Sloan
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism; D000279:Administration, Cutaneous; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D005260:Female; D006868:Hydrolysis; D051379:Mice; D008812:Mice, Hairless; D008954:Models, Biological; D009226:Myristates / Q000737:chemistry; D010539:Permeability; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis*; D012869:Skin Absorption; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D046509:Tissue Culture Techniques; D014867:Water / Q000737:chemistry
chemical_list: D018712:Analgesics, Non-Narcotic; D003692:Delayed-Action Preparations; D009226:Myristates; D011355:Prodrugs; D012997:Solvents; D014867:Water; C008205:isopropyl myristate; D000082:Acetaminophen