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  • Title: Delivery of nalbuphine and its prodrugs across skin by passive diffusion and iontophoresis.
    Author: Sung KC, Fang JY, Hu OY.
    Journal: J Control Release; 2000 Jun 15; 67(1):1-8. PubMed ID: 10773323.
    Abstract:
    The in vitro transport of nalbuphine (NA) and its prodrugs across various skins was investigated in order to assess the effects of prodrug lipophilicity on passive as well as iontophoretic permeation. The passive diffusion of NA and its prodrugs increased with the drug lipophilicity. Iontophoresis significantly increased the transport of NA and its prodrugs; the enhancement ratio was highest for NA and decreased as the drug lipophilicity increased. Measurements using intact and stratum corneum (SC)-stripped skins showed that the SC was the major skin diffusion barrier for the passive permeation of NA and nalbuphine pivalate (NAP). The iontophoretic permeation of NA and NAP across intact and SC-stripped skins indicated that the SC layer was not rate-limiting for the permeation of NA, but remained the rate-limiting barrier for transdermal permeation of NAP. Permeation studies using SC-stripped and delipidized skins suggested that the intercellular pathway was the predominant route for the passive permeation of NA and NAP as well as the iontophoretic permeation of NAP across the SC. The relative rates of passive and iontophoretic permeation across Wistar rat skins demonstrated that a significant amount of NA may permeate skin via the appendageal routes, whereas NAP permeated predominantly through the lipid matrix.
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