Some pharmaceutical and inclusion properties of 2-hydroxybutyl-β-cyclodextrin derivative.

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.