Interaction between surface active drug (FK906:rennin inhibitor) and cyclodextrins in aqueous solution.
The aggregation behavior of FK906, which is a peptide like hypertensive agent, in aqueous solution was studied by static light scattering, 1H-nuclear magnetic resonance (NMR), and surface tension. These experiments showed a clear critical micelle concentration (cmc) at around 6.3 x 10(-3) to 1.3 x 10(-2) M of FK906 aqueous solution. The result of 1H NMR experiments revealed that FK906 aggregates primarily by hydrophobic interactions involving the benzyl moiety. The Debye plots from light-scattering studies showed that the apparent molecular weight of aggregated FK906 molecule is 1670 which corresponds to 2-3 molecules of FK906. The effect of alpha- and beta-cyclodextrins on the surface tension of FK906 aqueous solution was investigated. It appeared that the addition of alpha-cyclodextrin showed very small shift of cmc, but that of beta-cyclodextrin shifted the cmc to much higher concentration. The investigation on the surface tension of FK906 aqueous solution in the presence of beta-cyclodextrin indicated that FK906 forms a 1:1 complex with beta-cyclodextrin. On the basis of these experiments, it appears that beta-cyclodextrin has an ability to change the surface active property of FK906 in its aqueous solution. Therefore, it is expected that the addition of beta-cyclodextrin to FK906 aqueous solution may prevent the adsorption onto container walls and/or reduce the local irritancy.
Analytical Research Laboratories, Fujisawa Pharmaceutical Co., Ltd. 1-6, Kashima 2-chome, Yodogawa-ku, Osaka 532-8514, Japan.
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Kitamura
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Fujimura
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Kohda
D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*; D004347:Drug Interactions; D006639:Histidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008027:Light; D008823:Micelles; D009025:Morpholines / Q000737:chemistry* / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D012542:Scattering, Radiation; D012996:Solutions; D013500:Surface Tension; D014867:Water / Q000737:chemistry; D000092502:Renin Inhibitors
D000959:Antihypertensive Agents; D003505:Cyclodextrins; D006639:Histidine; D008823:Micelles; D009025:Morpholines; D012996:Solutions; D014867:Water; D000092502:Renin Inhibitors; C083010:FK 906