ENHANCING EFFECT OF N-ACETYL-L-CYSTEINE OR 2-MERCAPTOETHANOL ON THE IN-VITRO PERMEATION OF 5-FLUOROURACIL OR TOLNAFTATE THROUGH THE HUMAN NAIL PLATE

The enhancing effects of various vehicles on the in,vitro permeation o f a hydrophilic model drug, 5-fluorouracil (5-FU), or a lipophilic mod el drug, tolnaftate (TN), through human nail plates were investigated using a modified side-by-side diffusion cell. Tip pieces from the 5th finger-nail, clipped from healthy volunteers, were used in this permea tion study. The swelling and softening properties of the nail pieces w ere also measured in each vehicle. The weights and stresses of the nai l pieces were dramatically changed after immersion in aqueous solvents containing N-acetyl-L-cysteine (AC) or 2-mercaptoethanol (ME). Howeve r, no significant change in the physicochemical properties of the nail pieces was found in the lipophilic vehicles. Thus, the water content in the nail plates absorbed from vehicles may relate to their physicoc hemical properties. Although keratin-softening agents and new skin per meation enhancers did not significantly promote 5-FU permeation compar ed with water alone, the flux from solvent systems containing A\C or M E was substantially higher. In addition, TN permeation from solvents c ontaining AC or ME could be measured, whereas that from other solvents was undetectable. When the AC concentration was increased, the 5-FU p ermeation and the nail weight increased and the stress of each nail pi ece decreased, It is concluded from these experimental results that AC and ME may be useful as enhancers for increasing drug permeation thro ugh the human nail plate.