Transdermal delivery of nalbuphine and nalbuphine pivalate from hydrogels by passive diffusion and iontophoresis

The objective of this study was to evaluate the in vitro transdermal permea tion of nalbuphine hydrochloride (CAS 23277-43-2) (NA) and nalpuphine pival ate (NAP), a novel prodrug of NA, from different hydrogel formulations unde r passive diffusion as well as iontophoresis. Various concentrations of pol ymers, including polyvinylpyrrolidone (PVP) and hydroxypropyl cellulose (HP C) were used in the hydrogel formulations. The passive permeation rate of N A was affected by the polymer concentrations, which can be attributed to di fferent viscosities of the hydrated formulations; whereas the passive perme ation rate of NAP was not influenced by the various polymer concentrations. Iontophoresis significantly increased the permeation rates of NA and NAP f rom various hydrogel formulations through skin; the enhancement ratios were higher for NA in all the formulations studied. The iontophoretic permeatio n rates of NA were slightly decreased by the incorporation of polymers; how ever, the transdermal flux and membrane potential were independent of polym er concentrations for both NA and NAP, demonstrating that the polymer conce ntrations in the hydrogel formulations did not have significant effects on the iontophoretic permeation of NA and NAP.