TY - JOUR
T1 - Altered skin permeation of a highly lipophilic molecule
T2 - tetrahydrocannabinol
AU - Touitou, Elka
AU - Fabin, Boris
PY - 1988/4
Y1 - 1988/4
N2 - The effect of decylmethylsulfoxide (decylMSO) and oleic acid on the skin permeation of the highly lipophilic compound, tetrahydrocannabinol (THC), was investigated. The solvents were propylene glycol (PG)-ethanol (EtOH) and PG-EtOH-H2O mixtures. For comparison, similar compositions containing the hydrophilic drug 5-fluorouracyl (5FU) were also tested. Twenty-four-hour experiments were performed with diluted solutions of the drugs in Valia-Chien diffusion cells through hairless mouse skin. The results were treated using the Transderm computer program. The results show that the permeability coefficient of THC was: (1) increased by an order of magnitude by water; (2) increased 6 times by 3% oleic acid in PG-EtOH solutions; (3) increased fourteen times by 3% oleic acid in PG-EtOH-H2O solutions; (4) not affected by decylMSO in PG-EtOH solutions; and (5) decreased 25% by decylMSO in PG-ETOH-H2O solutions. A different behavior was observed when similar systems containing the hydrophilic 5FU were tested. The permeability coefficient of 5FU was: (1) not affected by presence of water; (2) not affected by oleic acid; (3) not affected by decylMSO in PG-EtOH; and (4) increased 14 times by decylMSO in PG-EtOH-H2O. These results emphasize that the selective effect of an enhancer is the result of a tridimensional interaction between the drug, the skin, and the enhancer, in a specific environment.
AB - The effect of decylmethylsulfoxide (decylMSO) and oleic acid on the skin permeation of the highly lipophilic compound, tetrahydrocannabinol (THC), was investigated. The solvents were propylene glycol (PG)-ethanol (EtOH) and PG-EtOH-H2O mixtures. For comparison, similar compositions containing the hydrophilic drug 5-fluorouracyl (5FU) were also tested. Twenty-four-hour experiments were performed with diluted solutions of the drugs in Valia-Chien diffusion cells through hairless mouse skin. The results were treated using the Transderm computer program. The results show that the permeability coefficient of THC was: (1) increased by an order of magnitude by water; (2) increased 6 times by 3% oleic acid in PG-EtOH solutions; (3) increased fourteen times by 3% oleic acid in PG-EtOH-H2O solutions; (4) not affected by decylMSO in PG-EtOH solutions; and (5) decreased 25% by decylMSO in PG-ETOH-H2O solutions. A different behavior was observed when similar systems containing the hydrophilic 5FU were tested. The permeability coefficient of 5FU was: (1) not affected by presence of water; (2) not affected by oleic acid; (3) not affected by decylMSO in PG-EtOH; and (4) increased 14 times by decylMSO in PG-EtOH-H2O. These results emphasize that the selective effect of an enhancer is the result of a tridimensional interaction between the drug, the skin, and the enhancer, in a specific environment.
KW - Decylmethylsulfoxide
KW - Enhanced skin permeation
KW - Fluorouracyl-selective skin permeation
KW - Oleic acid
KW - Tetrahydrocannabinol
UR - http://www.scopus.com/inward/record.url?scp=0023904629&partnerID=8YFLogxK
U2 - 10.1016/0378-5173(88)90053-1
DO - 10.1016/0378-5173(88)90053-1
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AN - SCOPUS:0023904629
SN - 0378-5173
VL - 43
SP - 17
EP - 22
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -