Percutaneous absorption is strongly dependent upon the physicochemical properties of the active ingredient applied to skin—i.e., molecular weight (MW), liposolubility and octanol/water partition coefficient—and on the type and properties of the delivering vehicle. When this vehicle is based on lipid nanoparticulates, enhanced permeation has been reported. SLNs and NLCs are typical nanoparticulate carriers composed of physiological and biodegradable lipids. These carriers were reviewed in Parts I, II and III of this series, with respect to chemical content, production techniques and physicochemical characterization. The present installment, Part IV, discusses the percutaneous absorption of actives loaded into SLNs and NLCs and their formulation in dermal cosmetics. This series will be expanded to include an additional Part V, which will focus on the rheological and texture analysis of lipid nanoparticles.
Partitioning and Diffusion
The nature of a carrier vehicle is known to affect the depth of skin penetration of actives therein, owing to its role in solubility and release as well as its influence on transepidermal water loss. In parallel with in vitro and in vivo permeation studies, the thermo- dynamic activity of the active ingredient, i.e. the rate of transfer between the vehicle and the skin, must be assessed. More importantly than the concentration of active in a formulation, skin influx must be determined with respect to octanol/water partition coefficient, Km, which is the active ingredient distribution between a membrane, m, at equilibrium.
When an active is loaded in lipid matrices such as SLNs or NLCs, which are then dispersed in a semi-solid vehicle, e.g., o/w creams or hydrogels, the stratum corneum is the first layer with which it comes into contact. To be absorbed into the stratum corneum, the active must be released from the lipid matrix, diffuse in the vehicle, and reach the outermost layer of skin. Thus, the first critical step in determining the skin absorption level of the active is the partitioning between the particles and vehicle, and between the vehicle and the skin.