In vivo skin uptake of piroctone olamine in human subjects assessed by confocal Raman spectroscopy and tape stripping.

In vivo human studies are considered the gold standard for assessing skin penetration of actives. Tape stripping (TS) is a widely used method for investigating uptake of actives following topical application to the skin of human subjects. The results of TS studies have been shown to be influenced by a number of factors, including the variability in the amount of stratum corneum (SC) removed during the stripping process. This has stimulated much interest in the development of alternative non-invasive techniques for assessing skin penetration of compounds, such as confocal Raman spectroscopy (CRS). In the present work, in vivo skin delivery of piroctone olamine (PO) in human subjects was investigated from multiple solvent systems using CRS and TS. Vehicles were prepared with propylene glycol (PG), diethylene glycol monoethyl ether - Transcutol® (TC), isopropyl myristate (IPM), caprylic/capric triglycerides - Labrafac™ Lipophile WL 1349 (LAB) and propylene glycol monolaurate - Lauroglycol™ 90 (PGML). Analysis of CRS depth profiles, expressed as the area under the signal intensity-depth curve (AUC), showed higher PO uptake for PG:TC:IPM compared with PG:TC and PG:TC:LAB (p < 0.05). TS studies indicated higher total uptake of PO for PG:TC:IPM compared with PG:TC (p < 0.05). Across all formulations, linear correlations were observed between CRS-derived AUC values and TS-measured PO uptake (R2 = 0.79-0.99 for absolute uptake; 0.88-0.99 after protein normalization). To our knowledge, this is the first direct in vivo - in vivo correlation between CRS and TS for topical penetration of an active. It is also the first to investigate the in vivo skin uptake of PO using both CRS and TS, and to demonstrate correlations between these methods for profiling PO distribution within the SC.