Role of solvent in interactions between fatty acids-based formulations and lipids in porcine stratum corneum.

Fatty acids are commonly used as permeation enhancers to increase skin permeation of drug molecules by interacting with the intercellular lipids in the skin. The influences of the chain length of the fatty acid in different solvents on the stratum corneum (SC) lipids were investigated to further understand the mechanism of permeation enhancement of fatty acids. Gravimetric studies showed that SC absorbed propylene glycol (PG)-based formulations to a greater extent than mineral oil (MO)-based formulations and there was no correlation between the nature of fatty acid and the formulation uptake for PG-based formulations. High formulation uptake was only observed for MO-based formulation when more hydrophilic acids like acetic acid and propionic acid were added. Spectroscopic studies revealed that the vibrations of alkyl chains in the stratum corneum lipids were dependent on the solvent used. Fatty acids with short chains were able to perturb the SC lipids in lipophilic MO but not in PG based on symmetric peak shifts. For the PG-based formulations, skin perturbation was attained when long chain fatty acid such as oleic acid was present. The results showed that the nature of solvent played an important role in the interactions between the fatty acids and the intercellular lipids in the SC. These findings would make an important contribution to the choice of solvent in transdermal drug delivery systems.