Permeability physicochemical properties

Seventy years later, this theory largely holds true, although periodically challenged [67, 68]. Observation of transmembrane permeability of ionic species was initially explained by the formation of neutral ion-pair [69, 70]. A comprehensive review of the physicochemical properties influencing permeation has been written by Malkia et al. [5]. The reality is that, despite many studies, the effect of ionization on permeation is still a matter of discussion and active research. In contrast, it became clear that bulk-phase partitioning measurements are not adequate to describe bilayer partitioning [71-73]. 

Clearly the physicochemical properties of a drug are a decisive factor in its overall activity. Where possible, molecular structures should be optimized to obtain best clinical performance. Rarely does an oral drug have physicochemical features suitable for topical or transdermal therapy, and it can take a great deal of systematic research to identify where the best balance of activity and permeability lies. Experience with corticosteroids suggests that as much as a 100-fold improvement in clinical activity may be attainable through molecular design, for today s most potent topical corticosteroids are more active than hydrocortisone by a factor at least this large. 

Artursson, P., Application of physicochemical properties of molecules to predict intestinal permeability, AAPS Workshop on Permeability Dehnitions and Regulatory Standards, Arlington, VA, Aug. 17-19, 1998. 

Fagerholm, U., Lindahl, A., Lennernas, H., Regional intestinal permeability in rats of compounds with different physicochemical properties and transport mechanisms, /. Pharm. Pharmacol. 1997, 49, 687-690. 

---