Lecithin-linker microemulsions in transdermal delivery

Research on microemulsion-based transdermal delivery has been driven by the high solubilization capacity of lipophilic, hydrophilic and amphiphilic solutes, the large area/volume ratio for mass transfer, the potential for permeation enhancement, and the simplicity of manufacture of microemulsion-based products. Lecithin has been considered an ideal surfactant because of its biocompatibility, low toxicity and its ability to improve the uptake of drugs. Unfortunately, the tendency of lecithin to form liquid crystals and gels forced formulators to introduce toxic medium chain alcohols to deal with phase behavior issues. Later, the introduction of polymeric-type surfactants (polyethylene glycol or polyglycerol esters) in microemulsion formulations opened the doors to non-toxic, viscous, pharmaceutical grade, formulations. More recently, non-toxic, alcohol-free lecithin formulations have been obtained with linker additives that produce low viscosity formulas with high solubilization capacity. Linkers are surfactant-like compounds with asymmetric interactions. Sorbitan monooleate is an example of a lipophilic linker and partially ionized caprylic acid is an example of a hydrophilic linker. The combination of these linkers and lecithin produce microemulsions that exhibit high transdermal flux. This high flux is not explained by the increase in skin permeability, but by the increase in the concentration of the solute in the skin. This property was used to produce “in situ” patches that feature an extended release (> 12 hr) in vitro. Mathematical models and fluorescence probes further support that solute loading in the skin, mediated by the penetration of the lecithin, is the main reason for the enhanced transdermal flux. In vivo studies using cosmetic actives confirmed the low toxicity of lecithin-linker formulations and their ability to deliver lipophilic solutes.