Metrics and Clinical Relevance of Percutaneous Penetration and Lateral Spreading

Abstract

Background: Percutaneous penetration of urea in vivo in man has been documented. If urea can penetrate the skin, it may also move laterally. Lateral spreading of topical substances leads to unpredictable penetration dynamics and increased skin surface area exposure. Methods: The ability of urea, a low molecular-weight hydrophilic model, to penetrate the stratum corneum (SC) and spread outside the application site was investigated in vitro using tape stripping with spectroscopy. The parameters investigated were the following: time between urea application and tape stripping, formulations containing urea and use of a petrolatum-covered ring barrier around the marked application area. Results: The percentage of urea was determined in and around the application site. The spreading of topically applied urea to neighboring areas occurred and was time but not formulation dependent. A significant difference between protocols with and without the petrolatum ring was observed. Conclusion: These results suggest the clinical importance of lateral spreading, occurring predominately on the skin surface. SC thickness varies between anatomical sites, predisposing areas such as the face and scalp margins to increased percutaneous penetration of topical products. The use of a protective petrolatum ring can inhibit lateral spreading of hair dye in individuals allergic to hair dye, limit systemic absorption and increase accuracy when assessing penetration dynamics. © 2014 S. Karger AG, Basel

In vivo confocal Raman microscopic determination of depth profiles of the stratum corneum lipid organization influenced by application of various oils

“…The volunteers were instructed not to utilize any skin care products on the forearms at least 72 h and not to bath or shower at least 4 h before the beginning of the experiments. After an acclimation time of 20 min, 4 skin areas (each of 2 Â 2 cm 2 size) were marked on the volar forearms (2 areas on each arm) using a rubber barrier in order to exclude lateral spreading of the oils [51]. As a first step, the oil was topically applied on one marked area of the forearm and rubbed homogenously with soft rubber gloves.…”

Mitigation of nitrogen mustard mediated skin injury by a novel indomethacin bifunctional prodrug

“…In contrast, NM is hydrophilic; thus, direct application in solvents results in spreading over a relatively large area of skin. This makes quantification of tissue damage difficult to assess (Tewari-Singh et al, 2013; Tewari-Singh et al, 2014; Vieille-Petit et al, 2015). To address this problem, cutaneous patch models have been developed.…”

Predicting Transdermal Fentanyl Delivery Using Mechanistic Simulations for Tailored Therapy

“…Two computational domains were constructed: 1) a one-dimensional (1D) model, where the drug reservoir was as wide as the skin, so this simulated unidirectional drug transport ( Figure 2B ). This case is representative of Franz diffusion cell experiments ( Larsen et al., 2003 ; Rim et al., 2005 ; Bartosova and Bajgar, 2012 ) and has a low computational cost; 2) a three-dimensional (3D) model where the skin was wider than the drug reservoir to capture possible transverse diffusion of the drug (x and y directions in Figure 2A ), since the drug spreads laterally, the actual delivery surface area becomes larger than the patch surface area ( Vieille-Petit et al., 2015 ). The skin was extended by 1.7 mm [= 20 x (d sc + d vep )] on each side of the patch to avoid an impact of the transverse boundary on the simulated drug uptake kinetics at the interface between epidermis and dermis (surface 1 in Figure 2 ), as determined by a sensitivity analysis.…”