(M1330-10-55) Do We Emit Drugs through Our Skin?

Purpose: Generally, several volatile organic compounds (VOC) formed endogenously in the tissue due to metabolic and microbiome associated activities are emitted by the skin. The VOCs also include components that are in the systemic circulation. The objective of the project was to investigate if the components present systemically and distributed into the skin tissue would also undergo emission via the skin alongside other dermal VOCs.

Methods: Nicotine was selected as a model component for the investigation of potential trans-epidermal emission. The trans-epidermal emission of nicotine was investigated in vitro, using Franz diffusion cells across human cadaver skin. A modified diffusion cell was used to investigate the cross absorption as well. Human cadaver skin was used to investigate the emission of drugs. The drug solution was placed in the bottom compartment of the vertical diffusion cells and the top compartment was empty and was closed with a lid containing an adsorbent. The amount of drug that was emitted across the skin in the dermis to the stratum corneum and into the donor compartment was trapped using a strong adsorbent and subjected to analysis.

Results: There was a linear relationship between the concentration of nicotine in the subdermal compartment and the rate of nicotine emanated from the skin (R²=0.91) (Figure 1). The emanation of VOCs is analogous to the phenomenon of water evaporation across the skin (TEWL). The emanation of nicotine was enhanced 4-fold due to tape stripping (25 strips) from 0.002g/m²/h to 0.008g/m²/h. Pretreatment with the chemical permeation enhancers and mechanical rupture of the stratum corneum barrier using metallic microneedles also enhanced the rate of emanation of nicotine, similar to TEWL. Further, the potential for secondary absorption of drugs was investigated using a modified diffusion cell set up, for nicotine as well as for nitroglycerin. A significant amount of nicotine and nitroglycerin was found to undergo secondary absorption after emanation from the host skin (Figure 2)

Conclusion: It is evident from the results that people do potentially emanate drugs and other volatile organic compounds distributed in the skin. It is plausible that the emanated volatile organic compounds can be absorbed due to secondary exposure if conditions favor. The phenomenon of emanation of drugs and secondary absorption of drugs could impact pharmacokinetics and could be of concern if it could lead to significant levels in the secondary individual.

Acknowledgements: The authors acknowledge Topical Products Testing LLC, Oxford, MS for the funding support


Figure 1: The rate of emission of nicotine across the skin at different concentration of nicotine in the receiver compartment (n=6±s.d).


Figure 2: Secondary absorption of drugs after emanation from the source skin A) Nicotine B) Nitroglycerin S2 is secondary skin and R2 is secondary receiver medium (n=6±s.d).