EFFECT OF PH ON THE SKIN PERMEABILITY OF A ZWITTERIONIC DRUG, CEPHALEXIN

Skin permeability of the zwitterionic drug, cephalexin, was measured a t various pH. A U-shaped curve was obtained for the relationship betwe en the permeability coefficient and pH. Although cephalexin degraded d ependent on the pH, the concentration in the suspended donor solution was maintained constant by the high dissolution rate. The barrier func tion of skin, which was assessed by the permeation of the nonelectroly tes, cortisone and D-mannitol, did not change over the range from pH 3 .0 to 7.0. The permeability coefficient of cephalexin decreased with i ncrease in zwitterion fraction and decrease in fractions of cation and anion, suggesting that each ionic species has different skin permeabi lity. The permeability coefficient of zwitterion, estimated on this as sumption of each ionic species having different permeability, was abou t 10% that of cation and anion. The octanol/buffer distribution coeffi cient and diffusion coefficient were also lower for zwitterion than fo r cation and anion. This suggests that the pH dependency in skin perme ability of cephalexin may reflect the permselective property of skin d ependent on the lipophilicity and/or diffusivity of ionic species.