The effects of polar excipients transcutol and dexpanthenol on molecular mobility, permeability, and electrical impedance of the skin barrier

Abstract

In the development of transdermal and topical products it is important to understand how formulation ingredients interact with the molecular components of the upper layer of the skin, the stratum corneum (SC), and thereby influence its macroscopic barrier properties. The aim here was to investigate the effect of two commonly used excipients, transcutol and dexpanthenol, on the molecular as well as the macroscopic properties of the skin membrane. Polarization transfer solid-state NMR methods were combined with steady-state flux and impedance spectroscopy measurements to investigate how these common excipients influence the molecular components of SC and its barrier function at strictly controlled hydration conditions in vitro with excised porcine skin. The NMR results provide completely new molecular insight into how transcutol and dexpanthenol affect specific molecular segments of both SC lipids and proteins. The presence of transcutol or dexpanthenol in the formulation at fixed water activity results in increased effective skin permeability of the model drug metronidazole. Finally, impedance spectroscopy data show clear changes of the effective skin capacitance after treatment with transcutol or dexpanthenol. Based on the complementary data, we are able to draw direct links between effects on the molecular properties and on the macroscopic barrier function of the skin barrier under treatment with formulations containing transcutol or dexpanthenol.

Tracking solvents in the skin through atomically resolved measurements of molecular mobility in intact stratum corneum

“…One remarkable observation from the data in Fig. 5 is that PG has a stronger effect on inducing mobility in the amino acids in the terminal domains of keratin filament compared with a large number of other polar and apolar compounds investigated with this method (13,14). The addition of water to SC leads to increased mobility in both lipid and protein domains (Fig.…”

“…SC differs from most other biological membranes in that the main fraction of both lipids and proteins is solid at ambient conditions (10,11). Still, a minor fraction of lipids and protein components is mobile at physiological temperatures in conditions of hydrated SC, and after the addition of so-called moisturizers or penetration enhancers (6,(11)(12)(13)(14)(15). The macroscopic material properties of the SC barrier membrane naturally depend on the molecular properties of its building blocks.…”

“…In particular, transport properties as well as mechanical properties and water-holding capacity can be altered by changing the balance between solid and fluid structures in the complex SC material (13,14,(16)(17)(18)(19). Increasing fluidity is expected to lead to higher solubility and a higher diffusion coefficient for most added compounds, and thus increased effective SC permeability (14,18,19). A clear correlation between SC fluidity/molecular mobility and permeability of small molecules in SC has been demonstrated in previous studies (11-14, 16, 17, 20).…”

Topical use of dexpanthenol: a 70th anniversary article

“…A recent experimental study with excised porcine skin showed that dexpanthenol increases the molecular mobility of several lipid and protein segments of the stratum corneum thereby generating properties of a hydrated skin also in dehydrated conditions. Specifically, it has been demonstrated that dexpanthenol interacts with lipid segments of the extracellular lamellae and protein residues in the corneocytes in stratum corneum and thus compensates for reduced hydration by retaining/increasing molecular fluidity (21).…”

Brief Communication: Dexpanthenol and Its Ophthalmic Uses

“…Thus it generates properties of a hydrated skin in dehydrated conditions by increasing molecular fluidity [7].…”