Some pharmaceutical properties of 3-hydroxypropyl- and 2,3-dihydroxypropyl-beta-cyclodextrins and their solubilizing and stabilizing abilities.
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.
Yoshida
A
A
Yamamoto
M
M
Irie
T
T
Hirayama
F
F
Uekama
K
K
D003505:Cyclodextrins / Q000494:pharmacology*; D003912:Dextrins / Q000494:pharmacology*; D004355:Drug Stability; D005079:Excipients; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants; D012995:Solubility; D013213:Starch / Q000494:pharmacology*
D003505:Cyclodextrins; D003912:Dextrins; D005079:Excipients; D007509:Irritants; D013213:Starch