title: [In-vitro evaluation of cinnarizine as a competing agent to beta-cyclodextrin inclusion complexes: effect of cinnarizine on the membrane permeation rate of progesterone from its beta-cyclodextrin inclusion complex].
abstract: The use of competing agents is considered a powerful tool for the development of a drug-delivery system with drug/cyclodextrin inclusion complexes. However, there are very few studies examining this issue. To explain this phenomenon, it was thought that a competing agent with a sufficiently high stability constant had not yet been reported. In this study, cinnarizine (CN), which has a high stability constant with beta-cyclodextrin (beta-CD) and unique solubility characteristics, was selected, and its ability as a competing agent was examined in a membrane permeability study. The permeability study showed that the permeation rates of the drugs flurbiprofen, progesterone, and spironolactone decreased with their stability constants with the addition of beta-CD. In one of the drugs, progesterone (Pro), the decrease was restored by the addition of CN. The amount of CN added was a 1:1 molar ratio to the amount of Pro. However, no similar action was induced with the addition of DL-phenylalanine (Phe) in the permeation study at the 1:5 (Pro:Phe) molar ratio. These finding indicate that CN acts as a competing agent, and its action is much stronger than that of Phe.
authors.affiliation: Department of Drug Delivery Research, Hoshi University, Ebara, Shinagawa-ku, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Muraoka
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Tokumura
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Machida
mesh_terms: D001667:Binding, Competitive; D002936:Cinnarizine / Q000494:pharmacology*; D016503:Drug Delivery Systems; D008567:Membranes, Artificial; D010539:Permeability; D011374:Progesterone / Q000378:metabolism*; D047392:beta-Cyclodextrins
chemical_list: D008567:Membranes, Artificial; D047392:beta-Cyclodextrins; D002936:Cinnarizine; D011374:Progesterone