Utilization of prodrugs to enhance the transdermal absorption of morphine

TY - JOUR

T1 - Utilization of prodrugs to enhance the transdermal absorption of morphine

AU - Drustrup, J.

AU - Fullerton, A.

AU - Christrup, Lona Louring

AU - Bundgaard, H.

PY - 1991/1/1

Y1 - 1991/1/1

N2 - The feasibility of providing transdermal delivery of morphine was examined using the prodrug approach. Various alkyl esters formed at the 3- and/or 6-hydroxy group in morphine were prepared and their physico-chemical and skin penetration properties studied as well as their hydrolysis kinetics. The esters showed generally a higher water and lipid solubility than morphine and were also much more lipophilic than the parent drug in terms of octanol-buffer partition coefficients. Diffusion experiments in vitro using human skin samples showed that whereas morphine did not penetrate the skin to any measurable extent whether applied in the form of saturated solutions in water at pH 7.0 or in isopropyl myristate, the ester prodrugs showed a high penetrating capacity under the same conditions. Steady-state fluxes up to 35 μg morphine/cm per h were observed. For some esters essentially all of the amounts penetrated were present in the receptor phase as morphine. The study demonstrates the feasibility of achieving transdermal delivery of morphine based on the ready conversion and the favourable skin penetration properties of morphine esters which in turn are attributed to their combination of adequate water solubility and lipophilicity.

AB - The feasibility of providing transdermal delivery of morphine was examined using the prodrug approach. Various alkyl esters formed at the 3- and/or 6-hydroxy group in morphine were prepared and their physico-chemical and skin penetration properties studied as well as their hydrolysis kinetics. The esters showed generally a higher water and lipid solubility than morphine and were also much more lipophilic than the parent drug in terms of octanol-buffer partition coefficients. Diffusion experiments in vitro using human skin samples showed that whereas morphine did not penetrate the skin to any measurable extent whether applied in the form of saturated solutions in water at pH 7.0 or in isopropyl myristate, the ester prodrugs showed a high penetrating capacity under the same conditions. Steady-state fluxes up to 35 μg morphine/cm per h were observed. For some esters essentially all of the amounts penetrated were present in the receptor phase as morphine. The study demonstrates the feasibility of achieving transdermal delivery of morphine based on the ready conversion and the favourable skin penetration properties of morphine esters which in turn are attributed to their combination of adequate water solubility and lipophilicity.

UR - http://www.scopus.com/inward/record.url?scp=0025804950&partnerID=8YFLogxK

M3 - Journal article

AN - SCOPUS:0025804950

SN - 0378-5173

VL - 71

SP - 105

EP - 116

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1-2

ER -