ABSTRACT
Solid dispersions (SDs) containing the anthelmintic compound albendazole (ABZ) and either Pluronic 188 (P 188) or polyethylene glycol 6000 (PEG 6000) as hydrophilic carriers were formulated. Drug-polymers interactions in solid state were investigated using different techniques. Only a 4% of total ABZ was dissolved at 5 min post-incubation, reaching dissolution rates of 32.8% (PEG 6000) and 69.4% (P 188) in SDs. In this way, P 188 was substantially more efficient as ABZ dissolution promoter in comparison to PEG 6000, especially at the initial stages of the dissolution processes (<30 min). An increased systemic availability (p < 0.001) was obtained when ABZ was administered as ABZ-P 188 SDs, with a 50% enhancement in systemic exposure (AUC values) compared to treatment with an ABZ suspension. Consistently, the Cmax increased 130% (p < 0.001) following treatment with P 188 based SD ABZ formulation. For the ABZ-PEG 6000 SD formulation, the favorable effect on ABZ systemic availability did not reached statistical significance compared to the control group. The study reported here showed the utility of pharmacokinetic assays performed on mice as a model for preliminary drug formulation screening studies.
Subject(s)
Albendazole/chemistry , Albendazole/pharmacokinetics , Drug Carriers/chemistry , Albendazole/administration & dosage , Animals , Area Under Curve , Biological Availability , Chemistry, Pharmaceutical/methods , Drug Carriers/administration & dosage , Drug Carriers/pharmacokinetics , Drug Evaluation, Preclinical/methods , Male , Mice , Mice, Inbred BALB C , Polyethylene Glycols/chemistry , Solubility , Suspensions/administration & dosage , Suspensions/chemistry , Suspensions/pharmacokineticsABSTRACT
BACKGROUND: Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic compound. The parent FLBZ is metabolized to its reduced (R-FLBZ) and hydrolyzed (H-FLBZ) metabolites. There are no data on the potential nematodicidal activity of R-FLBZ, the main plasma metabolite found in sheep and mice. The goal of the current work was to assess the efficacy of FLBZ and R-FLBZ against Trichinella spiralis in a mouse model. METHODS: Both compounds were administered to Balb/c mice infected with T. spiralis as either a cyclodextrin aqueous solution or as a carboxymethylcellulose suspension. Treatments were performed orally (5 mg/kg) at 1 day after infection with T. spiralis. The efficacy of the treatments was assessed at day 6 after infection. RESULTS: While the efficacy obtained for FLBZ and R-FLBZ administered as a solution was 94 and 98%, respectively, the efficacies obtained after the treatment with FLBZ suspensions were 38% (FLBZ) and 64% (R-FLBZ). CONCLUSION: Under the current experimental conditions, a high nematodicidal efficacy of both FLBZ and R-FLBZ administered as solution preparations was observed.
