Physicochemical parameters, effect permeation

It is widely accepted that the two most important physicochemical parameters that determine a molecule s skin permeability are a) its lipophilicity, with a log (octanol/water partition coefficient) value of 2 being quite favorable, and b) its molecular size— smaller compounds permeating better than big ones. " Thus, it is no surprise that the passive transdermal delivery of peptides and proteins, which are typically either very polar (or charged) and/or of high molecular weight (>1000 Da), is extremely inefficient and rarely results in fluxes, which would elicit significant therapeutic effect. 

It must be re-emphaslzed at this point that the solubility parameter and Its use for quantifying physicochemical Interactions Is based on enthalplc considerations only entropic considerations are neglected. Consequently, while the Ideas outlined In this section provide a basis for membrane material selection (or at least for narrowing the number of possible choices), prediction of permeation and rejection remains elusive until the ability to predict effective transport corridor size 4 Is more firmly established. At that time the differences - 4, and ik, - i > can be used In conjunction with A and A for meiftrane Mterral... 

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