Abstract
Biological membranes, such as skin, eye cornea and the oral mucosa, form a lipophilic barrier towards drug permeation. Relatively lipophilic drugs are able to permeate these membranes by passive diffusion. However, passive diffusion is driven by high concentration of dissolved drug in the aqueous membrane exterior (e. g. tear fluid or saliva) or in aqueous drug vehicle (e. g. hydrogels or hydrophilic creams). Thus, greatest permeability should be obtained with drugs which are both lipophilic and highly soluble in the aqueous exterior. Hydrophilic water-soluble drugs are frequently unable to permeate the lipophilic membranes due to their inability to partition into the membrane. Lipophilic water-insoluble drugs are frequently unable to permeate the lipophilic membranes, or do it very slowly, due to very low concentration of dissolved drug in the aqueous exterior. It is possible to increase the permeability of lipophilic water-insoluble drugs through formation of water-soluble complexes [1]. For example, through formation of hydrophilic water-soluble cyclodextrin complexes of lipophilic water-insoluble drugs. This approach has been applied successfully in aqueous dermal formulations [2], mouthwash solutions [3], nasal spray formulations [4] and eye drop solutions [5].
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