Permeability-Solubility-Charge State and the pH Partition Hypothesis

1 PERMEABILITY-SOLUBILITY-CHARGE STATE AND THE pH PARTITION HYPOTHESIS 

Absorption and Drug Development Solubility, Permeability, and Charge State. By Alex Avdeef ISBN 0-471-423653. Copyright 2003 John Wiley Sons, Inc. 

Fick s first law applied to homogeneous membranes at steady state is a transport equation 

The limitation of Eq. (2.1) is that measurement of concentrations of solute within different parts of the membrane is very inconvenient. However, since we can estimate (or possibly measure) the distribution coefficients between bulk water and the membrane, log Kj (the pH-dependent apparent partition coefficient), we can convert Eq. (2.1) into a more accessible form 

The relevance of Eq. (2.2) (which predicts how quickly molecules pass through simple membranes) to solubility comes in the concentration terms. Consider sink conditions, where Ca is essentially zero. Equation (2.2) reduces to the following flux equation 

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