Metrics and clinical relevance of percutaneous penetration and lateral spreading.

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.