A protective effect against undesirable increase of dihydroetorphine permeation through damaged skin by using pressure-sensitive adhesive tape with an ethylene-vinyl acetate co-polymer membrane

The release kinetics of dihydroetorphine (DHE) from pressure-sensitive adhe sive (PSA) tape with an ethylene-vinyl acetate co-polymer (EVA) membrane as a diffusion-controlling membrane and its protective effect from an unpredi ctable increase in skin permeation of DHE caused by stratum corneum damage were investigated. The DHE dull through the EVA membrane was enhanced with the increase of vinyl acetate content. Although the DHE release from the PS A tape was proportional to the square root of the time, the release from th e PSA tape covered with the EVA membrane was dominated by zero-order rate, The release rate increased by the addition of isopropyl myristate to the PS A layer, due to the increase of solubility and diffusivity of DHE in the PS A. layer, and not a decrease of permeation resistance in the EVA membrane. When using the PSA tape with the EVA membrane, the steady-state flux of DHE through hairless rat skin with stratum corneum damage was not 2-fold more than that through non-damaged skin. Plasma DHE concentration rose promptly above 5 ng/ml after the application of the PSA tape onto the damaged skin i n hairless rat. In contrast, when the PSA tape with the EVA. membrane nas a pplied onto the damaged or non-damaged skin, plasma concentrations in the b oth cases were maintained in the therapeutic range (0.2-1.2 ng/ml). These r esults suggest that the PSA tape with the EVA membrane can be used to prote ct from the unpredictable increase in skin permeation of DHE due to stratum corneum damage.