The permeability of hairless mouse skin membrane to the weak base narcotic analgesic oxycodone (pKa = 8.53) was investigated. The effects of pH on the solubility and skin permeation rate were also studied. The results of the study of skin permeation of drug through hairless mouse skin suggest that the permeability of oxycodone base is approximately 7.4 times higher than that of protonated oxycodone. The nonionic species of oxycodone, at various drug loadings, was then incorporated in a Dow-Corning silicone elastomer for the evaluation of the release rate and skin permeation rate. It was found that Q/t1/2 is directly proportional to the square root of the drug loading dose, as expected by Higuchi's equation (where Q is the cumulative amount released and t is time). However, the skin permeation rate was observed to increase initially with drug loading and level off at the loading dose of 60 mg/cm3.