Improvement of oral bioavailability of fenbufen by cyclodextrin complexations.
The interactions of fenbufen (FB) with alpha-, beta-, gamma-cyclodextrins (CyDs) were studied in aqueous solution and in solid state. beta-CyD formed water soluble complex with FB in the molar ratio of 1:2 (guest:host). The solid complex of FB with alpha-CyD was obtained in the molar ratio of 1:2 (guest:host), while the same with gamma-CyD was obtained as 1:1 ratio. The dissolution rate and bioavailability of FB were significantly increased by the formation of inclusion complexes (alpha greater than gamma-CyD complex). CyDs had no effect on the metabolic time of FB forming two active metabolites, and the bioavailability of metabolites was also increased by complexation of FB with CyDs. The bitter taste of FB powder was reduced by alpha-CyD complexation. The enhanced bioavailability and reduced bitterness of FB by CyD complexations suggested the possibility of applying FB in smaller doses with fewer side-effects.
Miyaji
T
T
Research Laboratory, Lederle Co. Ltd, Saitama, Japan.
Inoue
Y
Y
Acartürk
F
F
Imai
T
T
Otagiri
M
M
Uekama
K
K
D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins; D007408:Intestinal Absorption; D010654:Phenylbutyrates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet
D003505:Cyclodextrins; D010654:Phenylbutyrates; C010725:fenbufen