Complexation and solubility behavior of albendazole with some cyclodextrins.
The main purpose of this work was to study the albendazole-cyclodextrins complexation equilibrium and to propose a suitable excipient to improve the solubility behavior and dissolution rate of albendazole. The complexation of albendazole with four cyclodextrins, alpha-CD, beta-CD, gamma-CD, and hydroxypropylated (HP)-beta-CD, has been studied by using electronic absorption spectroscopy and molecular mechanics. The equilibrium was studied at pH 7.5 under various temperature conditions, and at pH 1.8 with HP-beta-CD at 298 K. The albendazole binding constant was the greatest for the HP-beta-CD. Both the un-ionized (Alb) and the ionized species (AlbH+) were shown to interact with HP-beta-CD. The studies at different temperatures suggest that the hydrophobic effect is the most important driving force in these systems. Moreover, the dissolution rate studies with beta- and HP-beta-CDs in the buffered aqueous solution at pH 7.5 have been accomplished and the dissolution rate was observed to increase with the cyclodextrin concentration. The solubility behavior was studied with the Higuchi and Connors method. The phase solubility and direct spectroscopy methods reveal a 1:1 inclusion complex in all of the studied cases. Molecular mechanics data show the most probable structure of the complexes.
Díaz
D
D
Facultad de Química, Departamento de Química Inorgánica, UNAM, México D.F., México. david@servidor.unam.mx
Bernad Bernad
M J
MJ
Gracia Mora
J
J
Escobar Llanos
C M
CM
D015766:Albendazole / Q000008:administration & dosage* / Q000737:chemistry; D000871:Anthelmintics / Q000008:administration & dosage*; D003505:Cyclodextrins / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D012995:Solubility; D013696:Temperature
D000871:Anthelmintics; D003505:Cyclodextrins; D015766:Albendazole