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What is Log P?

The partition constant (P) provides us with a useful gauge of the degree of solubility of a molecule in a hydrophobic and hydrophilic environment. More specifically, P is defined as the ratio of the concentration of a particular compound in two solvents. The most common solvent pair used for such an experiment is an organic phase containing n-octanol and an aqueous phase consisting of water. Therefore, log P is the octanol-water partition coefficient. The expression for P is written as:

P = [Aorg]/[Aaq]

In this equation, the concentration of the solute that partitions in the organic and aqueous phase is given by [Aorg] and [Aaq], respectively. This equation can further be modified to its more common logarithmic form:

log P = log [Aorg] – log [Aaq]

Log P values are obtained empirically from this type of experiment. On the other hand, log P values may also be calculated by utilizing log P values for various fragments (e.g., functional groups) of a molecule (e.g., methylene, methyl, phenyl, ketone, carboxylic acid, amine, sulfhydryl, etc.) In general, there is fairly good agreement between experimental and calculated values.

A number of software packages include modules for calculating log P. For example, ACD Labs offers a log P calculator as part of the ACD/ChemSketch Freeware. In addition, one may find a similar calculator in ChemDraw, which is part of the ChemOffice Suite.

There has been considerable interest by people working in pharmaceutical and cosmetic science to use log P values to better understand the permeation behavior of transdermal administered drugs as well as skin care ingredients.1-2 There is some controversy over this subject, which is addressed by proponents of the Hansen solubility parameters.3 Nevertheless, a considerable amount of research is conducted using log P values to estimate the deliverability of a molecule to the skin.

References
1. R.O. Potts and R.H. Guy, Predicting skin permeability. Pharm. Res., 9, 663-669 (1992).
2. S. Grégoire S, C. Ribaud, F. Benech, J.R. Meunier, A. Garrigues-Mazert, and R.H. Guy, Prediction of chemical absorption into and through the skin from cosmetic and dermatological formulations. Br. J. Dermatol., 160, 80-91 (2009).
3. http://hansen-solubility.com/Skin.html