Stratum corneum polar drugs

A permeation enhancer can be defined as a compound that alters the skin barrier function so that a desired drug can permeate at a faster rate. Dozens of enhancers are patented each year, and several books have been written summarizing the work and proposing mechanisms of enhancement.70-72 The permeation enhancers may be classified simply as polar and nonpolar ones. They can be used individually or in combination, such as binary mixtures. For several drugs, the flux across skin was observed to be linear with that of the most widely used enhancer, ethanol.73-75 Another polar enhancer, isopropanol, facilitated ion association of charged molecules and enhanced the transport of both neutral and ionic species across the stratum corneum.76 77 While polar enhancers traverse the skin, nonpolar enhancers are largely retained in the stratum corneum both aspects make the combination a superior enhancer to the individual enhancers.78... 

If the drug stratum corneum/product partition coefficient K is defined as Csc(o)/C)>, CJc is assumed to be much less than Csc(o), and the permeability coefficient (kp) is KD/h, equation 4 is equivalent to equation 3. The lag time is normally defined by Fick s law as h2/6D. The importance of equation 4 is well illustrated by the work of Rougier and Lotte (1993) in which it was shown that the in vivo percutaneous absorption (= Js) of a series of compounds was directly related to their concentration in stripped stratum corneum, irrespective of their structure, concentration or site of application. In theory, drug transport could go via a polar pathway, with a permeability coefficient kp pojar, as well as through the intercellular lipid pathway, with a permeability coefficient kp iipi(1, although the existence of a polar pathway remains controversial. As indicated previously, for lipophilic drugs, an aqueous boundary layer is likely to be present at the stratum corneum-viable epidermis interface... 

---