Transport mechanisms permeation enhancers

Caco-2 cells have been valuable in the estimation of drug absorption potential, transport mechanisms, and effect of permeation enhancers on transepithelial transport.35,39,53,67-69,78-81 Owing to the sensitivity of the cells and the limited solubility of new molecular entities, Caco-2 permeability studies are routinely done with relatively low concentration of compounds. One way to increase the solubility of these compounds is to use organic solvents. The low tolerability of Caco-2 cells to organic solvents limits the use of this approach in permeability studies. 

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... 

Figure 5.4.4. Various liquid membrane permeation mechanisms. (After Marr and Kopp (1982).) (a) Simple permeation of sp des A (b) simple permeation enhanced by reaction of A with an agent E in permeate (c) facilitated transport with a reversible complexing agent B in the membrane (d) facilitated transport in the presence of a reactive agent E in permeate (e) countertransport (f) cotransport.

Abstract This chapter discusses the research and development of porous ceramic membranes and their application as membrane reactors (MRs) for both gas and liquid phase reaction and separation. The most commonly used preparation techniques for the synthesis of porous ceramic membranes are introduced first followed by a discussion of the various techniques used to characterise the membrane microstructure, pore network, permeation and separation behaviour. To further understand the structure-property relationships involved, an overview of the relevant gas transport mechanisms is presented here. Studies involving porous ceramic MRs are then reviewed. Of importance here is that while the general mesoporous natnre of these membranes does not allow excellent separation, they are still more than capable of enhancing reaction conversion and selectivity by acting as either a product separator or reactant distributor. The chapter closes by presenting the future research directions and considerations of porous ceramic MRs. 

---