Synthesis and characterization of water-soluble hydroxybutenyl cyclomaltooligosaccharides (cyclodextrins)

• Published in: Carbohydrate research Vol. 337; no. 6; pp. 493 - 507
• Main Authors: Buchanan, Charles M., Alderson, Susan R., Cleven, Curtis D., Dixon, Daniel W., Ivanyi, Robert, Lambert, Juanelle L., Lowman, Douglas W., Offerman, Rick J., Szejtli, Jozsef, Szente, Lajos
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 15.03.2002
• Subjects: Butanols - chemical synthesis; Butanols - chemistry; Carbohydrate Sequence; Chromatography, High Pressure Liquid; Cyclodextrin ether; Cyclodextrins - chemical synthesis; Cyclodextrins - chemistry; Glibenclamide; Glyburide - analogs & derivatives; Glyburide - chemical synthesis; Glyburide - chemistry; Guest–host complex; Hydroxybutenyl cyclodextrin; Hydroxybutenyl cyclomaltooligosaccharide; Ibuprofen; Ibuprofen - analogs & derivatives; Ibuprofen - chemical synthesis; Ibuprofen - chemistry; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Oligosaccharides - chemical synthesis; Oligosaccharides - chemistry; Solubility; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Water - chemistry; Guest–host complex; Hydroxybutenyl cyclomaltooligosaccharide; Hydroxybutenyl cyclodextrin; Glibenclamide; Cyclodextrin ether; Ibuprofen
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(01)00328-7

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-β-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. Graphic