Some pharmaceutical properties of 3-hydroxypropyl- and 2,3-dihydroxypropyl-.BETA.-cyclodextrins and their solubilizing and stabilizing abilities.

Abstract

3-Hydroxypropyl- and 2,3-dihydroxypropyl-.beta.-cyclodextrins (3-HP- and DHP-.beta.-CyDs) with different degrees of substitution (D.S.) were prepared and their pharmaceutical properties were investigated. The aqueous solubility of 3-HP- and DHP-.beta.-CyDs was much higher than that of the parent .beta.-CyD and the dissolution of DHP-.beta.-CyD in water was endothermic. The acid-and .alpha.-amylase-catalyzed hydrolysis rates of 3-HP- and DHP-.beta.-CyDs were slower than those of the parent .beta.-CyD. The hemolytic activity (human erythrocytes) and local irritancy (rabbit muscle) of DHP-.beta.-CyD were considerably less than those of natural, methylated or other hydroxyalkylated .beta.-CyDs, and decreased with increasing D.S. The ability of the hydroxyalkylated .beta.-CyDs to remove cholesterol and proteins from human erythrocytes decreased with increasing D.S., and correlated well with their hemolytic activity. 3-HP-.beta.-CyD was a more effective solubilizer for poorly water-soluble drugs than the parent .beta.-CyD, and its stabilizing effect on chemically instable drugs was higher than that of the parent .beta.-CyD. The above data suggest a considerable pharmaceutical potential of 3-HP- and DHP-.beta.-CyDs as parenteral carriers.