betadex and flubendazole

The bioavailability of the anthelminthic flubendazole was remarkably enhanced in comparison with the pure crystalline drug by developing completely amorphous electrospun nanofibres with a matrix consisting of hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone. The thus produced formulations can potentially be active against macrofilariae parasites causing tropical diseases, for example, river blindness and elephantiasis, which affect altogether more than a hundred million people worldwide. The bioavailability enhancement was based on the considerably improved dissolution. The release of a dose of 40 mg could be achieved within 15 min. Accordingly, administration of the nanofibrous system ensured an increased plasma concentration profile in rats in contrast to the practically non-absorbable crystalline flubendazole. Furthermore, easy-to-grind fibers could be developed, which enabled compression of easily administrable immediate release tablets.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; Animals; beta-Cyclodextrins; Biological Availability; Chemistry, Pharmaceutical; Crystallization; Mebendazole; Nanofibers; Povidone; Rats; Tablets

The goal of elimination of the human filariases would benefit greatly from the use of a macrofilaricidal agent. In vivo trials in humans and many experimental animal models suggest that flubendazole (FLBZ) is a highly efficacious macrofilaricide. However, since serious injection site reactions were reported in humans after parenteral FLBZ administration, the search for alternative pharmaceutical strategies to improve the systemic availability of FLBZ and its metabolites has acquired urgency in both human and veterinary medicine. The goal of the current work was to compare the systemic exposure of FLBZ formulated as either an aqueous hydroxypropyl-β-cyclodextrin (CD) or aqueous carboxymethyl cellulose (CMC) suspension or a Tween 80-based formulation (TWEEN) in rats and jirds (Meriones unguiculatus). Healthy animals of both species were allocated into four experimental groups of 44 animals each: FLBZ-CD oral and FLBZ-CDsc, treated with the FLBZ-CD formulation by the oral or subcutaneous routes, respectively; FLBZ-TWEENsc, dosed subcutaneously with the FLBZ-TWEEN formulation; and FLBZ-CMC oral, treated orally with the FLBZ suspension. The FLBZ dose was 5 mg/kg. FLBZ and its hydrolyzed (H-FLBZ) and reduced (R-FLBZ) metabolites were recovered in plasma samples collected from rats and jirds treated with the different FLBZ formulations. In both species, FLBZ parent drug was the main analyte recovered in the bloodstream. In rats, FLBZ systemic exposure (AUC 0-LOQ) was significantly (P < 0.05) higher after the FLBZ-CD treatments, both oral (4.8 ± 0.9 µg.h/mL) and subcutaneous (7.3 ± 0.6 µg.h/mL), compared to that observed after oral administration of FLBZ-CMC suspension (0.93 ± 0.2 µg.h/mL). The same differences were observed in jirds. In both species, parenteral administration of FLBZ-TWEEN did not improve the systemic availability of FLBZ compared to FLBZ-CDoral treatment. In conclusion, formulation approaches that enhance the availability of flubendazole in the rat and jird may have therapeutic implications for a drug with poor or erratic bioavailability.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Antinematodal Agents; beta-Cyclodextrins; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Gerbillinae; Mebendazole; Rats; Rats, Wistar

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Anthelmintics; beta-Cyclodextrins; Brugia; Chemistry, Pharmaceutical; Diethylcarbamazine; Drug Therapy, Combination; Elephantiasis, Filarial; Excipients; Filaricides; Humans; Ivermectin; Mebendazole; Onchocerca volvulus; Onchocerciasis

Cystic echinococcosis (CE) is an important public health problem worldwide. Flubendazole, administered in tablets, has shown poor in vivo efficacy against CE in humans. However, flubendazole prepared as a solution caused a marked reduction in hydatid cysts developed in mice. The goal of the current work was to compare the chemoprophylactic effect of flubendazole formulated either as a hydroxypropyl-β-cyclodextrin solution or as a carboxymethylcellulose suspension in secondary CE in mice.. Balb/C mice were infected with Echinococcus granulosus protoscoleces. One day after infection, the animals were allocated into 3 different experimental groups: unmedicated control and treated at the time point of infection with flubendazole either prepared as a solution or suspension given twice a day during 15 days. Six months after infection, the animals were sacrificed to collect and weight parasitic cysts. Cyst samples recovered from infected mice of each experimental group were prepared for both scanning and transmission electron microscopy.. Both flubendazole formulations induced a significant reduction in cyst weight compared to the cysts recovered from the unmedicated control animals. Both formulations showed similar flubendazole-induced ultrastructural morphological changes.. Flubendazole offers a great potential to become a drug of choice in the preventive treatment of cystic echinococcosis.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Antinematodal Agents; beta-Cyclodextrins; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Disease Models, Animal; Echinococcosis; Mebendazole; Mice; Mice, Inbred BALB C; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission

Flubendazol is a veterinary antiparasitic agent which acts toxically on both adult and larval stages of round worms. It is nearly insoluble in water and it influences not only the selection of the dosage form, but also its biological availability. Its solubility can be increased by adding solutizers and tensides, or by complex-formation with cyclodextrins. In the published experimental paper the method of complex-formation of flubendazol with 2-hydroxypropyl-beta-cyclodextrin was employed and the effect of temperature on the resultant solubility of the active ingredient was examined. The final dosage form was pellets produced with the use of the method of extrusion and spheronisation.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Antinematodal Agents; beta-Cyclodextrins; Chemistry, Pharmaceutical; Cyclodextrins; Mebendazole; Pharmaceutic Aids; Solubility; Temperature