Some Pharmaceutical Properties of 2,3,6-partially Methylated-β- cyclodextrin and its Solubilizing and Stabilizing Abilities

Abstract

The pharmaceutical properties of 2,3,6-partially methylated-β-cyclodextrin(PMCD) were investigated. The aqueous solubility of PMCD was much higher than that of the parent βCyD, and it exhibited endothermic dissolution in contrast to that of the conventional heptakis-(2,6-di-O-methyl)-β-cyclodextrin(DMCD). The acid-catalyzed hydrolysis rate of PMCD was faster than those of the parent β-CyD and DMCD. The hemolytic activity (human erythrocytes) of PMCD was similar to that of DMCD. PMCD was a more effective solubilizer for poorly water-soluble drugs than the parent β-CyD; however PMCD is not as effective as DMCD. The stabilizing effect of PMCD on chemically unstable drugs was higher than that of the parent β-CyD. For 2,3,6 partially methylated-β-CyD(PMCD), in which the hydroxyl groups of cyclodextrin are substituted by a methyl group, the methylation ratios are as follows: 58–62% at the 2-position, 48∼52% at the 3-position, and 98∼100% at the 6-position1). This novel cyclodextrin derivative is synthesized by MERCIAN CORPORATION2). The aqueous solubilities of conventional heptakis-(2,6-di-O-methyl)-β-cyclodextrin(DMCD) and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin(TMCD) usually decreased with increasing temperature; however, PMCD exhibited endothermic dissolution in a manner similar to that of the parent β-cyclodextrin (PCyD). PMCD has received considerable attention in the pharmaceutical field; therefore, in this study some of the physicochemical properties of PMCD, such as surface activity, hemolytic activity and chemical stability in acid medium were investigated. In addition, the solubilizing and stabilizing abilities of PMCD for pooly water-soluble drugs were compared with those of β-CyDand DMCD.