Abstract
Skin penetration enhancers reversibly decrease the barrier resistance of the stratum corneum and allow drugs to penetrate more readily to the viable tissues and the systemic circulation. This paper presents a general theory for accelerant activity based on possible alterations at the molecular level of the components of the horny layer. Within the intercellular route, enhancers may interact at the polar head groups of the lipids, within aqueous regions between lipid head groups, and between the lipophilic tails of the bilayer. Inside the corneocyte it is the keratin fibrils and their associated water that are the targets. High concentrations of solvents may also alter partitioning processes. Because of the involvement of lipid and protein modifications, together with partitioning phenomena, the scheme of possible enhancer interactions has been termed the Lipid Protein Partitioning (LPP) theory. This theory is applied specifically to water, Azone, dimethylsulphoxide, dimethylformamide, 2–pyrrolidone, N-methyl-2–pyrrolidone, oleic acid, decylmethylsulphoxide, sodium lauryl sulphate and propylene glycol.