No abstract

The improved pharmacokinetic performance observed for the novel formulation of ABZ correlated with an improved in vivo therapeutic response against a model intestinal nematode parasite in dogs.

New therapeutic strategies based on the search of alternative formulations of albendazole (ABZ) and albendazole sulphoxide (ABZSO) are under current development to optimize posology and antiparasite efficacy in dogs. In an incomplete block design, nine dogs were randomly divided into three groups (n = 6). Treatments were carried out in two phases as follows. Phase I: Group I (treatment A), animals received ABZ at 25 mg/kg of conventional formulation. Group II (treatment B), dogs received 25 mg/kg of a modified poloxamer-ABZ formulation. Group III (treatment C), animals were treated with ABZSO in equimolar amount to ABZ doses. After 21 days of wash-out period the experiment was repeated (Phase II). Blood samples were collected over 24 h and subsequently analysed by high performance liquid chromatography. ABZSO and ABZSO(2) were the analytes recovered in plasma. Significant higher (P < 0.001) ABZSO area under the concentration-time curve (+500%) and C(max) (+487%) values were obtained for the treatment C in comparison with treatments A and B. However, no statistical differences on pharmacokinetic parameters were found between formulations A and B. In conclusion, the enhanced plasma concentration profile obtained for the ABZSO formulation used in treatment C may contribute to optimize the anthelmintic control in dogs.

The main objectives of this study were (a) to evaluate the in vitro performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b) to study the in vivo pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The in vivo assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form.

The aim of this study was to evaluate the influence of different matrices developers on the pharmacokinetic behavior of Ricobendazole (RBZ) controlled release (CR) formulations and test their correlation in vitro-in vivo, using one Albendazole (ABZ)-based and one RBZ-based immediate-release formulation as references. The main excipients used for CR formulations were Hydroxypropyl Methyl Cellulose, Cetyl Alcohol, Gelucire 50/02 ® and Alginic Acid. Pharmacotechnical quality control tests were successfully completed. Twelve parasite-free no pregnant dogs were randomly divided into six groups and received different treatments (single oral doses) using an incomplete block design (two phases) (n=4). Phase I: treatment "A" (ABZ-based immediate-release formulation [25 mg/kg]). Treatment "B" (RBZ-based immediate release formulation [20 mg/kg]) and treatments from "C" to "F" (CR formulations [20 mg/kg]). Phase II was performed after 21 days of washout period. Blood samples were collected over 48 h and analysed by UV High Performance Liquid Chromatography. In vitro dissolution profiles showed that matrices agents favored a reservoir effect. Active metabolite Albendazole sulphoxide (ABZSO) or Ricobendazole (RBZ) plasma exposure measured in terms of area under concentration vs time curve (AUC) of all RBZ formulations was greater (p<0,05) when compared with that obtained for ABZ reference formulation. No statistical differences in AUC values were found among all RBZ formulations assayed (p>0.05). Nevertheless, RBZ-Cetyl alcohol formulation showed a statistical difference on its time peak concentration (p<0.05). In conclusion the results obtained in vitro do not correlate with those obtained in vivo, being this work useful to identify other matrices developers in RBZ-CR formulations.