In-vitro transdermal permeation of oxycodone: (I) effect of PH, delipidization and skin stripping

Abstract

The effect of pH, skin stripping and delipidization on the in-vitro transdermal permeation of a weak base analgesic, oxycodone (pKa=8.53), was studied using hydrodynamically calibrated Valia-Chien diffusion cells. Saturated oxycodone. HCl solutions in citrate-phosphate buffers ranging from pH 4 to 10 were used as the donor solution. Skin samples from the abdominal and dorsal sites of hairless rats, abdominal site of hairless mouse, rabbit pinna ear, as well as human cadaver skin were used in permeation studies. The pHs at which maximum flux attained varied from 6.5 to 7.5 depending upon animal model. The permeabilities of protonated form through intact skin of all the animal models used, was about 7-15 fold lower than that of nonionic form. The unexpected high permeation rate at pHs ranges 4 to 6.5 across human cadaver could be attributed to the possible damage upon storage. The skin stripping and delipidizaton process appeared to increase the permeation rates of oxycodone and the degree enhancement is dependent upon the pH in the donor compartment.