Peracylated beta-cyclodextrins as novel sustained-release carriers for a water-soluble drug, molsidomine.
Peracylated beta-cyclodextrins with different alkyl chains (acetyl-octanoyl) were prepared by acylating all hydroxyl groups of beta-cyclodextrin (beta-CyD), and their physical properties were evaluated. These hydrophobic beta-CyDs decreased the release rate of molsidomine, a peripheral vasodilator, in proportion to the lengthening of alkyl chain and suppressed a peak plasma level of molsidomine following oral administration of peracylated beta-CyD complexes to dogs. Among the peracylated beta-CyDs tested, perbutanoyl-beta-CyD maintained sufficient plasma drug levels for a long period of time, while other peracylated beta-CyDs having shorter or longer chains were inappropriate to control the in-vivo release behaviour of molsidomine. The prominent retarding effect of perbutanoyl-beta-CyD was ascribable to the appropriate mucoadhesive property and hydrophobicity, compared with other peracylated beta-CyDs. The present results suggest that perbutanoyl-beta-CyD is particularly useful in modifying the release rate of water-soluble drugs as a novel slow-release carrier.
Uekama
K
K
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Horikawa
T
T
Yamanaka
M
M
Hirayama
F
F
D000215:Acylation; D000284:Administration, Oral; D000818:Animals; D002214:Capsules; D003505:Cyclodextrins / Q000737:chemistry; D003692:Delayed-Action Preparations; D004285:Dogs; D004337:Drug Carriers; D008297:Male; D008981:Molsidomine / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water; D047392:beta-Cyclodextrins
D002214:Capsules; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D014867:Water; D008981:Molsidomine; C031215:betadex