Physicochemical properties of drugs and membrane permeability

Drug penetration across membranes is complex and dependent on many possible physicochemical interactions. The main physicochernical determinants include partition, the molecular weight and size of the drug molecule, its solubility, ionization state, and hydrogen-bonding capacity. These and molecular conformational descriptors and their role in quantitative structure permeability relationships (QSPR) are discussed in this review. The identification and quantification of these factors and their inclusion in predictive QSPR algorithms, based on an understanding of the physicochernical properties that govern membrane permeation, facilitate the selection of new drugs and formulations.