Design and in-vitro characterization of new ricobendazole controlled release tablets

PAREDES, A.; DIB A; ALLEMANDI, D.; SANCHEZ BRUNI S.; PALMA S.

Congreso; II Reunión Internacional de Ciencias Farmacéuticas (RICIFA), Rosario; 2012

Design and in-vitro characterization of new Ricobendazole controlled release tablets Paredes AJ1*, Dib AR2, Sanchez Bruni SF3, Allemandi DA1, Palma SD1 1UNITEFA-CONICET, Departamento de Farmacia, Facultad de Ciencias Químicas, UNC, Argentina. 2Laboratorio de Farmacología, Facultad de Medicina Veterinaria, UdelaR, Uruguay. 3Laboratorio de Farmacología, FCV, UNCPBA, Argentina (aparedes@fcq.unc.edu.ar)   Introduction   Worldwide distributed, endoparasite diseases (ED) are a real important issue in humans and domestic animals, being able to originate varied symptomatology, from loss of appetite to death of the parasitized hosts depending on their parasitic load. Monogastric animals are generally treated with various doses of commercially available single-dose forms of Albendazole. In this context, the development of sustained release formulations becomes important to obtain constant plasma concentrations. Ricobendazole (RBZ), the sulfoxide metabolite of Albendazole (ABZ) is widely used for the treatment of endoparasites in domestic animals. RBZ shows higher bioavailability when compared with ABZ, being necessary to control its release rate in order to avoid toxicity1. A natural polymer and a lipid were used in two concentrations to moderate drug delivery from the designed tablets2,3(P2.5, P5 and L7.5, L15 respectively). The components of each formulation are shown in table 1#.   Materials and Methods   RBZ was obtained from Todo Droga®, Argentina. All excipients used in this work were pharmaceutical grade. The lipid was grounded, deeply frozen and immediately granulated in an oscillating granulator from Erweka®. 500mg tablets were obtained by wet granulation and compressed with a single punch tablet machine from TS®, Argentina. Friability, hardness, content uniformity and weight uniformity assays were carried out under FA specifications. Controlled release (CR) formulations were compared with an immediate release tablet used as a control (F1). Dissolution studies were performed in 900mL of HCl 0.1N at 37°C. Basket method was used to avoid flotation at 50rpm. Samples (5mL) were withdrawn at 5, 10, 15, 30, 60, 120, 240, 360 and 480 minutes with replacement of fresh medium, filtered and suitably diluted. Drug concentration was determined spectrophotometrically.   Results   Table 2 shows the pharmacotechnical data of RBZ tablets. The developed formulations showed excellent mechanical properties (high hardness, low friability) with very good appearance. A high weight and content uniformity were observed in all formulations. A rapid dissolution rate of RBZ was observed in the control formulation. The polymer based tablets delivered 50% of RBZ at 60 minutes while the lipid tablets did it at 360 minutes.   Discussion/Conclusion   CR tablets were succesfully developed. Both the lipid and the polymer effectively modulated drug release being the lipid formulations which had the lowest dissolution rate. Lipid concentration was in agreement with drug release rate but polymer concentration did not show the same behavior. The relationship between the simplicity on the manufacturing process and the advantages of this type of CR formulations represent an optimum option for the treatment of ED in domestic animals.