title: Synthesis and characterization of water-soluble hydroxybutenyl cyclomaltooligosaccharides (cyclodextrins).
abstract: We have examined the synthesis of hydroxybutenyl cyclomaltooligosaccharides (cyclodextrins) and the ability of these cyclodextrin ethers to form guest-host complexes with guest molecules. The hydroxybutenyl cyclodextrin ethers were prepared by a base-catalyzed reaction of 3,4-epoxy-1-butene with the parent cyclodextrins in an aqueous medium. Reaction byproducts were removed by nanofiltration before the hydroxybutenyl cyclodextrins were isolated by co-evaporation of water-EtOH. Hydroxybutenyl cyclodextrins containing no unsubstituted parent cyclodextrin typically have a degree of substitution of 2-4 and a molar substitution of 4-7. These hydroxybutenyl cyclodextrins are randomly substituted, amorphous solids. The hydroxybutenyl cyclodextrin ethers were found to be highly water soluble. Complexes of HBen-beta-CD with glibenclamide and ibuprofen were prepared and isolated. In both cases, the guest content of the complexes was large, and a significant increase in the solubility of the free drug was observed. Dissolution of the complexes in pH 1.4 water was very rapid, and significant increases in the solubility of the free drugs were observed. Significantly, after reaching equilibrium concentration, a decrease in the drug concentration over time was not observed.
authors.affiliation: Eastman Chemical Company, Research Laboratories, Kingsport, TN 37662, USA. buck@eastman.com
authors.forename: Charles M
authors.initials: CM
authors.lastname: Buchanan
authors.forename: Susan R
authors.initials: SR
authors.lastname: Alderson
authors.forename: Curtis D
authors.initials: CD
authors.lastname: Cleven
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Dixon
authors.forename: Robert
authors.initials: R
authors.lastname: Ivanyi
authors.forename: Juanelle L
authors.initials: JL
authors.lastname: Lambert
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Lowman
authors.forename: Rick J
authors.initials: RJ
authors.lastname: Offerman
authors.forename: Jozsef
authors.initials: J
authors.lastname: Szejtli
authors.forename: Lajos
authors.initials: L
authors.lastname: Szente
mesh_terms: D000440:Butanols / Q000138:chemical synthesis* / Q000737:chemistry*; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry*; D005905:Glyburide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D007052:Ibuprofen / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry*; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014867:Water / Q000737:chemistry*
chemical_list: D000440:Butanols; D003505:Cyclodextrins; D009844:Oligosaccharides; C021705:maltooligosaccharides; D014867:Water; D005905:Glyburide; D007052:Ibuprofen