Oral bioavailability in sheep of albendazole from a suspension and from a solution containing hydroxypropyl-beta-cyclodextrin.
Albendazole (ABZ) is a benzimidazole derivative with a broad spectrum of activity against human and animal helminthe parasites. ABZ has a very poor aqueous solubility. This study shows that hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is able to form inclusion complexes with ABZ and that is able to increase its aqueous solubility. A synergistic effect exists between HP-beta-CD and citric acid. The combination of HP-beta-CD (200 mM) and citric acid (50 mM) allows dissolution of more than 1.5 mg of ABZ per ml. The aim of this study is the in vivo evaluation in sheep of a solution of the inclusion complex of ABZ with HP-beta-CD in comparison with a suspension of the same drug. A significant (P<0.05) increase in the relative bioavailability is obtained with the solution containing the ABZ-HP-beta-CD complex as measured by ABZSO plasma levels. The area under the curve (AUC(0--> proportional, variant )) of the solution is 37% higher than that obtained with the suspension. Likewise the peak plasma concentration (C(max)) is twice that of the solution while the time to reach C(max) (T(max)) is reduced.
Evrard
B
B
Lab of Pharmaceutical Technology, Institute of Pharmacy, University of Liège, CHU-Tour 4, Bât B36, Avenue de l'Hôpital 1, 4000 1, Liège, Belgium. b.evrard@ulg.ac.be
Chiap
P
P
DeTullio
P
P
Ghalmi
F
F
Piel
G
G
Van Hees
T
T
Crommen
J
J
Losson
B
B
Delattre
L
L
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019999:Pharmaceutical Solutions; D012756:Sheep; D012995:Solubility; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D019999:Pharmaceutical Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D015766:Albendazole