title: Quantitative evaluation of aqueous isopropyl alcohol enhancement on skin flux of terbutaline (sulfate). 2. Permeability contributions of equilibrated drug species across human skin in vitro.
abstract: This paper demonstrates the usefulness of an equilibria-cotransport model for understanding the isopropyl alcohol-enhanced transport of an ionizable model compound, terbutaline in its sulfate salt form, through human skin in vitro. With the same isopropyl alcohol concentrations (0 - 80% v/v) present at both sides of skin, the permeation experiments were conducted using split-thickness skin and dermis membranes. The equilibria-cotransport model was consistent with total terbutaline flux and a terbutaline-to-sulfate flux ratio, both increased with increasing isopropyl alcohol and/or terbutaline sulfate concentrations. From the saturated drug solutions, aqueous isopropyl alcohol enhanced terbutaline skin flux about 10 - 100-fold with the maximum at 60 - 80% isopropyl alcohol. This overall flux enhancement was qualitatively separated into the contributions of isopropyl alcohol effects on both equilibrated donor concentrations and skin permeabilities of protonated terbutaline, terbutaline-sulfate ion pair anion, and neutral terbutaline-sulfate (2:1) ion triplet. In addition to altering the species equilibria, isopropyl alcohol was found to enhance the transport of both neutral and ionic species of terbutaline sulfate across stratum corneum.
authors.affiliation: Pharmaceuticals Division, CIBA-GEIGY Corporation, Suffern, NY 10901, USA.
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.forename: T K
authors.initials: TK
authors.lastname: Bergstrom
mesh_terms: D000433:1-Propanol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010539:Permeability; D012867:Skin / Q000187:drug effects*; D013726:Terbutaline / Q000494:pharmacology*
chemical_list: D000433:1-Propanol; D013726:Terbutaline