Novel 3-O-pegylated carboxylate and 3-O-pegylated carbamate prodrugs of naltrexone for microneedle-enhanced transdermal delivery.
A small library of novel 3-O-pegylated carboxylate prodrugs (4a-4b) and 3-O-pegylated carbamate prodrugs (9a-9b) of naltrexone were synthesized. The goal behind the design of these prodrugs was to investigate their potential for microneedle-enhanced transdermal delivery. All the synthesized 3-O-pegylated carboxylate prodrugs (4a-4b) and 3-O-pegylated carbamate prodrugs (9a-9b) of naltrexone were found to have adequate stability in a transdermal formulation and improved apparent solubility compared to naltrexone. Viscosity effects were postulated to be responsible for the observed non-linearity in the flux-concentration profile of these prodrugs.
Yerramreddy
Thirupathi Reddy
TR
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Milewski
Mikolaj
M
Penthala
Narsimha Reddy
NR
Stinchcomb
Audra L
AL
Crooks
Peter A
PA
D000279:Administration, Cutaneous; D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry*; D009271:Naltrexone / Q000008:administration & dosage* / Q000737:chemistry; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000737:chemistry; D009339:Needles; D011355:Prodrugs / Q000008:administration & dosage*; D012995:Solubility; D013552:Swine; D013556:Swine, Miniature; D014783:Viscosity
D002264:Carboxylic Acids; D009292:Narcotic Antagonists; D011355:Prodrugs; D009271:Naltrexone
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