TY - JOUR

T1 - Enhanced transdermal delivery of ketobemidone with prodrugs

AU - Hansen, L.B.

AU - Fullerton, A.

AU - Christrup, Lona Louring

AU - Bundgaard, H.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - The feasibility of achieving transdermal delivery of the opioid analgesic ketobemidone was assessed in human skin penetration studies in vitro using both ketobemidone itself and three carbonate ester prodrugs formed at the phenolic hydroxyl group. Whereas ketobemidone itself only showed a limited ability to permeate the skin from either polar or apolar vehicles the ester prodrugs very readily penetrated through the skin from solutions in isopropyl myristate and, in particular, from ethanol and ethanol-water solutions. Thus, steady-state fluxes in the range of 40-140 μg ketobemidone base/cm per h were observed for the ketobemidone esters from 20% w/v solutions in ethanol and ethanol-water (3:1 and 1:1 v/v) vehicles. The esters were rapidly hydrolyzed to the parent drug in the presence of skin enzymes and only from ketobemidone was detected in the receptor phase. The study demonstrates the feasibility of achieving transdermal delivery of ketobemidone based on the ready enzymatic conversion and the favourable skin penetration properties of the ester prodrugs which in turn are attributed to their high solubilities in both polar and apolar solvents.

AB - The feasibility of achieving transdermal delivery of the opioid analgesic ketobemidone was assessed in human skin penetration studies in vitro using both ketobemidone itself and three carbonate ester prodrugs formed at the phenolic hydroxyl group. Whereas ketobemidone itself only showed a limited ability to permeate the skin from either polar or apolar vehicles the ester prodrugs very readily penetrated through the skin from solutions in isopropyl myristate and, in particular, from ethanol and ethanol-water solutions. Thus, steady-state fluxes in the range of 40-140 μg ketobemidone base/cm per h were observed for the ketobemidone esters from 20% w/v solutions in ethanol and ethanol-water (3:1 and 1:1 v/v) vehicles. The esters were rapidly hydrolyzed to the parent drug in the presence of skin enzymes and only from ketobemidone was detected in the receptor phase. The study demonstrates the feasibility of achieving transdermal delivery of ketobemidone based on the ready enzymatic conversion and the favourable skin penetration properties of the ester prodrugs which in turn are attributed to their high solubilities in both polar and apolar solvents.

UR - http://www.scopus.com/inward/record.url?scp=0026702702&partnerID=8YFLogxK

U2 - 10.1016/0378-5173(92)90163-V

DO - 10.1016/0378-5173(92)90163-V

M3 - Journal article

AN - SCOPUS:0026702702

VL - 84

SP - 253

EP - 260

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 3

ER -