Improvement of some pharmaceutical properties of DY-9760e by sulfobutyl ether β-cyclodextrin

Abstract

The interaction of DY-9760e, a novel cytoprotective agent, with sulfobutyl ether β-cyclodextrin (SBE-β-CyD) in phosphate buffered saline (PBS) at various pH and ionic-strengths was studied by spectroscopic methods and the solubility method, and the results were compared with that of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD). The circular dichroism (CD) spectroscopic studies suggested that both β-CyDs form the inclusion complexes with DY-9760e in a molar ratio of 1:1, and the interaction of DY-9760e with SBE-β-CyD is much stronger than that with HP-β-CyD at any pH studied, in terms of a synergetic effect of hydrophobic and electrostatic interactions. The different intermolecular interaction between the SBE-and HP-β-CyD complexes was clearly reflected in the stability constant ( K′), e.g. the different dependence of K′ value on pH and ionic strength of solutions. 1H- and 13C-NMR studies suggested that HP-β-CyD interacts preferably with the benzene ring of DY-9760e, whereas SBE-β-CyD interacts not only with the benzene ring via hydrophobic interaction but also with the piperazine ring of the drug via electrostatic interaction. The solubilizing ability of SBE-β-CyD against DY-9760e was much greater than that of HP-β-CyD at any pH studied. Furthermore, SBE-β-CyD markedly suppressed the photo-degradation of DY-9760e in aqueous solution and reduced the adsorption of DY-9760e from PBS to polyvinyl chloride (PVC) tubes after incubation. The results suggest that SBE-β-CyD is useful in preparing parenteral solutions of poorly water-soluble drugs with positive charge such as DY-9760e.