Is the permeability coefficient K_p a reliable tool in percutaneous absorption studies?

Abstract

In percutaneous absorption studies the potency of penetration of chemical substances is often described by the permeability coefficient K_p. The experimentally determined K_p is characterized according to Fick’s first law of diffusion by the ratio of flux and the concentration of the test compound (K_p=Flux/C). This equation implies that in percutaneous absorption studies K_p is theoretically a more reliable parameter than flux taking the concentration into consideration, and should remain constant for each compound independent from the grade of dilution. In our study we evaluated the course of the percutaneous absorption parameters flux and K_p of neat and of 50% aqueous solution of 2-butoxyethanol (BE). An infinite dose of neat and 50% aqueous solution of non-radiolabeled BE were applied on excised human skin from two donors in static diffusion cells in parallel (for each test setting n=21). The flux of 50% aqueous BE (0.704±0.152 mg/cm²/h) was about 15-fold higher than that of neat BE (0.045±0.014 mg/cm²/h). The comparison of the K_p values of both test settings showed with a factor of about 31 (K_p=1.563×10^–3 cm/h) much higher values for 50% aqueous BE and K_p=0.050×10^–3 cm/h for neat BE. Although the flux does not consider the chemical concentration, it showed a smaller difference in both test settings as K_p; however, the flux remains a non-specific parameter for the description of percutaneous absorption. The results of our experiments showed that the permeability coefficient K_p was not able to adjust the flux of BE to the concentration. This is in agreement with the evaluation of K_p from BE data described in the literature.