Skin penetrating abilities and reservoir effects of neat DMF and DMF/water mixtures

This study was set out to determine the skin permeabilities of neat N, N-dimethylformamide (DMF, denoted as DMF100%) and DMF/water mixtures (including 50% DMF/50% water and 10% DMF/90% water mixtures (v/v), denoted as DMF50% and DMF10%, respectively) and to assess their skin reservoir effects on the systemic absorption. The penetration fluxes for DMF10% and DMF50% (= 0.015 and 0.126 mg/cm2/h, respectively) were only ~ 1.1%and 15% in magnitude as that of DMF100% (= 0.872 ± 0.231 mg/cm2/h), respectively. The above results could be because the perturbation effect of the DMF content was much more significant than the rehydration effect of the water content on skin permeability. We found that 85.9%, 96.6% and 98.7% of applied doses were still remaining on the skin surface, 4.98%, 0.838% and 0.181% were still remaining in the skin layer, and 9.09%, 2.61% and 1.17% penetrated through the skin layer after the 24-h exposure for DMF100%, DMF50% and DMF10%, respectively. We found that the half-life (T1/2) of DMF retaining in the skin layer were 12.3, 4.07 and 1.24 h for DMF100%, DMF50% and DMF10%, respectively. The estimated reservoir effect for DMF100% (=  34.1%) was higher than that of DMF50% and DMF10% (= 27.1% and 14.1%, respectively). The above results suggest that the impact associated with the internal burden of DMF could be prolonged even the external exposure of DMF is terminated, particularly for those dermal contact with DMF/water mixtures with high DMF contents.