Use of theoretical partition coefficients determined from solubility parameters to predict permeability coefficients for 5-fluorouracil.

Values for experimental permeability coefficients of 5-fluorouracil (5-FU) in 7 single- and 4 two component vehicles were determined from flux measurements through hairless mouse skin in diffusion cells and from solubility data. Theoretical partition coefficients of 5-FU between vehicle and skin were determined from solubility parameters of drug, vehicle, and skin, and from this theoretical permeability coefficients were estimated. Comparison of theoretical with experimental values for the permeability coefficients showed a good correlation for vehicles with solubility parameters between 12-18 (cal/cm3)1/2. For vehicles or mixtures of vehicles with solubility parameters in the range of 8-12 (cal/cm3)1/2, increases in flux and permeability coefficients were seen compared with theoretical predictions, possibly due to the similarity in solubility parameters of the vehicles to that of skin (10 cal/cm3)1/2. There was an inverse relationship between 5-FU solubility in the vehicles and flux or permeability coefficient that corresponded approximately to the point where the solubility parameters of drug and vehicle were the same.