Transdermal Oxymorphone Formulation Development and Methods for Evaluating Flux and Lag Times for Two Skin Permeation-Enhancing Vehicles

Oxymorphone is a candidate for transdermal delivery since it is a very potent analgesic, is not very effective orally, and has a short duration of action. In developing a transdermal delivery system, two criteria that were considered important were achieving adequate flux and minimizing the lag time. Oxymorphone skin permeation rates in vitro were very low unless skin permeation enhancers were included in the vehicle. After an initial screen of 17 formulations, two skin permeation-enhancing formulations were selected for further study. These were myristic acid:propylene glycol:oxymorphone base (A), and decylmethylsulfoxide:ethanol:water:oxymorphone • HCI (B). With either formulation and either human or hairless guinea pig skin, there was little dependence of either in vitro flux or lag time on the section of skin used (stratum corneum, epidermis, epidermis/dermis). There were significant differences between human skin and hairless guinea pig skin when comparing in vitro fluxes with the two formulations. With formulation A, fluxes through hairless guinea pig skin were three- to fivefold greater than through human skin. With B, however, fluxes through human skin were up to fivefold greater than through hairless guinea pig skin. In vitro lag times with A were generally long (≈24 h), whereas those with B were much lower (≈1 to 10 h). The species dependence of permeation enhancement and the differences in lag time between formulations could be related to differences in the mechanisms of permeation enhancement. In vivo lag times with the fatty acid:propylene glycol vehicle were estimated in hairless guinea pigs based on plasma oxymorphone concentrations. These were much lower than in vitro lag times.