Effect of chemical structure on nonelectrolyte penetration of oral mucosa.
The in vitro permeability of oral mucosa from New Zealand rabbits to 17 nonelectrolytes was studied using radioactive tracer techniques. Calculated permeability coefficients were independent of solute concentration and were similar when measured from outer to inner surface or inner to outer surface. Generally, an increase in chain length and increased lipid solubility within a series of alcohols or diols resulted in increased permeability. However, the first member of each series displayed anomalous behavior in that it penetrated more rapidly than the second member of the series. Addition of one or more hydroxyl groups to a compound brings about a decrease in permeability. The addition of a second or third hydroxyl group has less of an effect in decreasing permeability if it is adjacent to an existing hydroxyl as compared to when it is further separated. Addition of a hydroxyl group to a compound decreases permeability to a greater extent than addition of a ketone. Also, replacement of a hydroxyl group with an amide results in decreased permeability. These results point out the importance of lipid solubility and ability to form hydrogen bonds to permeability.
D000438:Alcohols / Q000378:metabolism; D000818:Animals; D006018:Glycols / Q000378:metabolism; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D009061:Mouth Mucosa / Q000378:metabolism*; D010539:Permeability; D011817:Rabbits; D012995:Solubility; D013329:Structure-Activity Relationship; D014508:Urea / Q000378:metabolism
D000438:Alcohols; D006018:Glycols; D014508:Urea