Effect of pH on the skin permeability of a zwitterionic drug, cephalexin

Abstract

Skin permeability of the zwitterionic drug, cephalexin, was measured at various pH. A U-shaped curve was obtained for the relationship between the permeability coefficient and pH. Although cephalexin degraded dependent on the pH, the concentration in the suspended donor solution was maintained constant by the high dissolution rate. The barrier function of skin, which was assessed by the permeation of the nonelectrolytes, cortisone and o-mannitol, did not change over the range from pH 3.0 to 7.0. The permeability coefficient of cephalexin decreased with increase in zwitterion fraction and decrease in fractions of cation and anion, suggesting that each ionic species has different skin permeability. The permeability coefficient of zwitterion, estimated on this assumption of each ionic species having different permeability, was about 10% that of cation and anion. The octanol/buffer distribution coefficient and diffusion coefficient were also lower for zwitterion than for cation and anion. This suggests that the pH dependency in skin permeability of cephalexin may reflect the permselective property of skin dependent on the lipophilicity and/or diffusivity of ionic species.