title: Some pharmaceutical and inclusion properties of 2-hydroxybutyl-β-cyclodextrin derivative.
abstract: 2-Hydroxybutyl-β-cyclodextrins (HB-β-CyDs) with different degrees of substitution (D.S.) were prepared and their physicochemical and biological properties and solubilizing abilities were studied and compared with those of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD). The surface activity of HB-β-CyD was higher than that of HP-β-CyD (D.S. 5.6) and increased with its concentration and D.S. The moisture sorption of HB-β-CyD (D.S. 5.5) was less than that of HP-β-CyD (D.S. 5.6), because of the introduction of hydrophobic hydroxybutyl groups in a molecule. The hemolytic activity (rabbit erythrocytes) decreased in the order of 2,6-di-O-methyl-β-cyclodextrin (DM-β-CyD)>methyl-β-cyclodextrin (M-β-CyD)>HB-β-CyD (D.S. 5.5)>β-CyD>HP-β-CyD (D.S. 5.6). The hemolytic activity of HB-β-CyD increased with D.S. and HB-β-CyD induced echinocyte (or crenation), as well as DM-β-CyD does. It was suggested from the solubility study of membrane components that HB-β-CyD interacted predominantly with cholesterol in erythrocytes, resulting in the hemolysis. The inclusion ability of HB-β-CyD was higher than that of HP-β-CyD (D.S. 5.6), especially for poorly water-soluble drugs with long linear structures such as biphenylylacetic acid and flurbiprofen (FP). For example, HB-β-CyD formed the inclusion complex with FP in a molar ratio of 1:1, by including the biphenyl moiety in the host cavity. The dissolution rate of FP/HB-β-CyD (D.S. 5.5) complex was faster than that of HP-β-CyD (D.S. 5.6) complex. The results suggested that HB-β-CyDs have considerable pharmaceutical potential and can work as a fast-dissolving carrier for poorly water-soluble drugs.
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Ishiguro
authors.forename: Eri
authors.initials: E
authors.lastname: Morishita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iohara
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Hirayama
authors.forename: Koki
authors.initials: K
authors.lastname: Wada
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
authors.forename: Kaneto
authors.initials: K
authors.lastname: Uekama
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry*; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D010648:Phenylacetates / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D013329:Structure-Activity Relationship; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D005079:Excipients; D010648:Phenylacetates; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C012776:biphenylylacetic acid; D005480:Flurbiprofen