Preparation and characterization of albendazole beta-cyclodextrin complexes

Albendazole (ABZ), mebendazole (MBZ), and ricobendazole (RBZ) are low-solub le anthelmintic benzimidazole carbamate drugs. To increase their aqueous so lubility, three different types of beta-cyclodextrins (CyDs): beta-cyclodex trin (CD), hydroxypropyl-beta-cyclodextrin (HPCD), and methyl-beta-cyclodex trin (MCD) were used. Solubility depended on the type of CyDs. Increased so lubility was obtained when the more substituted CyDs (HPCD or MCD) were use d instead of nonsubstituted CD. Stability constants were calculated assumin g a 1:1 stoichiometry. Calculated stability constant values depended on ini tial solubility of drug and pH of the medium. Solid ABZ complexes were prep ared by coprecipitation and freeze-drying methods. These products were comp ared with physical mixtures of ABZ and CyDs. The characterization of these products was made by differential scanning calorimetry (DSC) and drug relea se studies. True inclusion complexes were obtained only by the freeze-dryin g method. Drug release studies showed that the freeze-dried inclusion compl exes increased the solubility rate of ABZ, although a supersaturation effec t was observed when drug release studies were performed in nonsink conditio ns. A bioavailability study on mice was done with a formulation of ABZ:HPCD complex and was compared to a conventional ABZ suspension. A significantly (p < .05) shorter T-max of absorption was obtained by using the complex fo rmulation. Greater and significant (p < .05) differences for AUC and C-max were observed.