Predicting the Percutaneous Penetration of Cosmetic Ingredients

By: Sara Farahmand, PhD, University of Cincinnati College of Pharmacy; and Howard I. Maibach, MD, PhD, University of California School of Medicine

Posted: March 30, 2010, from the April 2010 issue of Cosmetics & Toiletries.

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The issue is complicated further if the composite nature of log K_oct is considered, because it contains a degree of information regarding hydrogen bonding. Although no proven collinearity of variables was detected in the adopted models in the present study, a poor insignificant correlation between log K_oct and HA (r: −0.361, p > 0.05) was found. The poor correlation coefficient does not demonstrate that log K_oct and HA are independent. If C_max was an indication of drug permeation rate, a negative correlation between C_max and HA could be expected.

The positive correlation of HA and Cmax from Eq. 4 and 5 suggests considering C_max as a complex parameter composed of absorption and elimination. If a high number of hydrogen bonding acceptor groups can impede the skin permeation, its effect on the clearance process also should be noted. The affinity of the drugs to body fluids, which affects the volume of distribution, is partly related to their molecular properties, such as hydrogen bonding.

Assuming a linear single compartment model, the total amount of drug in the blood may be expressed as Eq. 6.

dS/dt = −k*S + A*J     Eq. 6

In Eq. 6, k is the sum of the various elimination rate constants, A is the patch area, and J is the flux of drug across the skin.¹¹ An increased number of hydrogen bond acceptor groups may decrease J, but also may increase k. Therefore its net effect on blood concentration should be noted. Moreover, the effects of hydrogen bonding capacity on protein binding and metabolism may also interfere with plasma concentration.