Buscador de Personas - SIGEVA - Universidad Nacional de Córdoba

Introduction Chagas disease (CD) is a tropical infectious disease caused by the intracellular flagellate protozoan Trypanosoma cruzi. Nowadays, it remains a serious public health problem in several Latin American Nations and was included by the World Health Organization in the group of ?neglected diseases?. In Argentine, it is estimated that close to 7.6 million people would find exposed to the disease and about 1.6-2.0 million infected. The Chagas National Program has estimate that every year born about 1.300 new infected.1 Benznidazole (BZN) is commonly used as the primary therapeutic agent and it can eliminate the symptoms associated with the acute phase, providing a satisfactory cure rate (efficacy ≥ 80%).2 The highest efficacy of pharmacotherapy was observed during children and early adolescence treatment. Unfavorable pharmacokinetic properties, such as poor water solubility, short terminal half-time and limited tissue penetration, lead to irregular oral absorption and promote an erratic bioavailability. In addition, numerous adverse reactions have been reported (4 to 30 %)3 due to high toxicity and gastrointestinal intolerance which often lead to discontinuation of therapy. Currently, many efforts are being made to ensure the provision of medicines for the treatment of CD4, however, there is still no suitable pharmaceutical formulation for the treatment on pediatric patients. In this context, this work focuses on the development and in vitro evaluation of BNZ formulations containing pediatric doses under chewable tablet form, with taste masked and rapid drug dissolution in order to improve the patient compliance and unfavorable pharmacokinetic of BNZ. Materials and Methods BZN was extracted and purified from commercial tablets (Radanil®, 100mg of BZN, Roche, Arg.). All GRAS (Generally Recognized As Safe) excipients were selected as fillers, sweetners, flavors and disgregrants, after previous preformulation studies (data not shown). Four batches of tablets, containing 12.5, 25, 50 and 100mg of BZN (F1, F2, F3, F4 respectively), were manufactured using a single punch tablet machine (SC3, Talleres Sanchez®). Disintegration time, friability, hardness, weight and content uniformity, and dissolution assays (1000mL HCl 0.1N, paddle at 75rpm and 37°C) were carried out, according US Pharmacopeia specifications. Commercial tablets of Radanil®, BZN 100mg were used as reference. Preliminary drug-excipients compatibility was evaluated by thermal analysis (DSC and TG). Results Table 2 shows the pharmacotechnical data of chewable formulations. All batches showed excellent mechanical properties (high hardness, low friability) with very short disintegration times (<5 min). A high weight and content uniformity were observed. From dissolution studies, rapid dissolution rates of BZN (Q80% ≤ 15 min) were observed. Thermal studies of formulations showed no drug-excipient interactions. Discussion/Conclusion A new alternative for the treatment of CD was developed under chewable tablet form, containing 12.5, 25, 50 and 100mg of BZN with improved pharmacotechnical and biopharmaceutical behavior when compared with available commercial formulations. Furthermore, an efficient masked and sweet flavor was achieved after tablet administration, which could contribute to improve patient acceptability and treatment efficacy. References Programa Nacional de Chagas. Ministerio de Salud. Presidencia de la Nación. Acceso: Abril, 2012. Disponible en: http://www.msal.gov.ar/chagas/index.php/institucional/diagnostico 2S. Sosa Estani, E. Segura. Etiological treatment in patients infected by Trypanosoma cruzi: experiences in Argentina. Curr. Opin. Infect. Dis. 19, 583 ? 587 (2006). 3S. Sosa Estani, EL. Segura, AM. Ruiz, E. Velázquez, B. Porcel, C. Yampotis. Chemotherapy with benznidazole in children in undetermined phase of Chagas disease. Am J Trop Med Hyg; 59, 526-9 (1998). 4Lamas MC, Maggia NG, Orlandi S, Paredes AJ, Salomon CJ, Jimenez-Kairuz AF, Tarragona S. Diseño y preparación de formas farmacéuticas sólidas y líquidas de benznidazol para el tratamiento de la Enfermedad de Chagas, Informe Consolidado, Estudio Colaborativo Multicéntrico. Comisión Nacional Salud Investiga, Ministerio de la Nación Argentina. 1-62 (2011).

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