Altered skin permeation of a highly lipophilic molecule: tetrahydrocannabinol

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.