Author Junginger, H.E.; Verhoef, J.C.
low molecular weight transmucosal penetration enhancers for improved absorption of hydrophilic drugs (e.g. peptides and proteins), related mechanisms of action, novel types of macromolecular penetration enhancers, such as anionic polyacrylates and cationic chitosan and chitosan derivatives, have been developed. These polymers can enhance the paracellular permeability of mucosal epithelia (intestinal, nasal) by transiently opening the tight junctions, thereby increasing the paracellular absorption of hydrophilic and macromolecular drugs. Neither of these two classes of polymers interact with mucosal cell membrane components and consequently do not enhance transcellular transport of hydrophilic compounds, polyacrylates and chitosan derivatives show no acute toxicity and are not absorbed, these characteristics favor the conclusion that both types of polymers are safe penetration enhancers for transmucosal delivery of hydrophilic drugs and offer promising prospects for novel pharmaceutical applications, Cell membranes of the mucosal linings consist of phospholipid bilayers in which proteins for signal transfer are incorporated. These cell membranes are barriers to macromolecules and to most polar compounds, but they are relatively permeable to water and small hydrophobic molecules. Methods to facilitate transport of molecules, either small or large, across epithelial cells, Mechanisms of action of penetration enhancers (absorption promoters) can influence the mucosa in different ways: By acting on the mucous layer, By acting on the membrane components, By acting on the tight junctions, absorption enhancers are functional excipients included in formulations to improve the absorption of a pharmacologically active drug. The term absorption enhancer usually refers to an agent whose function is to increase absorption by enhancing membrane permeation, rather than increasing solubility, so such agents are sometimes more specifically termed permeation enhancers, advanced absorption enhancers currently in development and the formulation technologies, barriers to absorption and the mechanisms by which those barriers can be surmounted is presented. Factors influencing the success of absorption-enhancing formulations, absorption enhancement has also been applied to delivery by the transmucosal and transdermal routes, the agents and technologies are mainly those that alter drug permeation through the biological membrane that acts as the barrier to absorption, active ingredient is not chemically altered, but is combined with another agent or a specific formulation composition to increase permeability. Technologies that enhance absorption by increasing dissolution or solubility, absorption-enhancing technologies
