"One long-standing approach for improving transdermal drug delivery uses penetration enhancers (also called sorption promoters or accelerants) which penetrate into skin to reversibly decrease the barrier resistance. Numerous compounds have been evaluated for penetration enhancing activity, including sulphoxides (such as dimethylsulphoxide, DMSO), Azones (e.g. laurocapram), pyrrolidones (for example 2-pyrrolidone, 2P), alcohols and alkanols (ethanol, or decanol), glycols (for example propylene glycol, PG, a common excipient in topically applied dosage forms), surfactants (also common in dosage forms) and terpenes. Many potential sites and modes of action have been identified for skin penetration enhancers; the intercellular lipid matrix in which the accelerants may disrupt the packing motif, the intracellular keratin domains or through increasing drug partitioning into the tissue by acting as a solvent for the permeant within the membrane. Further potential mechanisms of action, for example with the enhancers acting on desmosomal connections between corneocytes or altering metabolic activity within the skin, or exerting an influence on the thermodynamic activity/solubility of the drug in its vehicle are also feasible, and are also considered in this review."

"When we try to maximize drug flux through the skin, we usually meet major difficulties because of the impervious nature of the stratum corneum. A popular solution incorporates penetration enhancers into transdermal products. Such materials ideally possess the sole property of reversibly reducing the barrier resistance of the horny layer, allowing the drug to reach the living tissues at a greater rate. This article considers examples of accelerant action that support a general concept explaining enhancer activity in human skin. The core of the proposal is that enhancers usually work by one or more of three main mechanisms: alteration of the lipid or protein domains of the stratum corneum or increase in tissue partitioning of a drug, a coenhancer, water, or any combination of these three chemicals. We may usefully refer to the overall hypothesis as the lipid-protein-partitioning (LPP) concept."