ABSTRACT
INTRODUCCIÓN: En Argentina se emplea el benznidazolcomo terapéutica de primera línea para el tratamiento etiológico del Chagas. Desde su lanzamiento (hace más de 40 años), sólo se dispone de comprimidos convencionales de 100 mg; no se han desarrollado nuevas formas farmacéuticas que aumenten la eficacia y seguridad, ni alternativas con dosis pediátricas. OBJETIVOS: Desarrollar formas farmacéuticas de benznidazol que ofrezcan ventajas farmacoterapéuticas. MÉTODOS: Preformulación y diseño de nuevas formulaciones de benznidazol, con caracterización físico-química y selección de las formulaciones más favorables. Frente a la discontinuidad de producción del ingrediente activo benznidazol, se desarrolló una metodología de extracción a partir de 8520/8520/nica alternativa comercial disponible. RESULTADOS: Se obtuvieron nuevas formulaciones de comprimidos de 50 y 100 mg debenznidazol, con una rápida disolución del producto de referencia. Además, se obtuvieron formulaciones masticables de 50 mg bajo la forma de hidrogeles azucarados, con un efectivo enmascaramiento del mal sabor. Todas las formulaciones cumplieron los ensayos de evaluación de las propiedades farmacotécnicas y biofarmacéuticas, superando los perfiles de referencia. CONCLUSIONES: Se desarrollaron nuevas alternativas farmacéuticas de benznidazol de rápida disolución, que podrían mejorar el tratamiento etiológico de la enfermedad(especialmente en pediatría) y convertirse en herramientas aptas para su explotación comercial
INTRODUCTION: In Argentina, benznidazole is the drug of choice for the etiological treatment of Chagas disease. Since it was launched (more than 40 years ago), there are only 100 mg tablets available; the development included neither new pharmaceutical forms improving efficacy and safety, nor a pediatric dosage option. OBJECTIVES: To develop pharmaceutical form sof benznidazole with pharmacotherapeutic advantages. METHODS: Preformulation and design of new formulation sof benznidazole, with physicochemical characterization and selection of the most favorable formulations. Due to the discontinuity in the production of the active ingredient benznidazole, a specific methodology was developed in order to obtain it from the only commercially available alternative. RESULTS: New benznidazole tablet formulations were obtained (50 and 100 mg), with a rapid dissolution of the reference product, as well as chewable formulation sof 50 mg as sugar hydrogels featuring an effective taste masking. All formulations passed the evaluation tests for pharmacotechnical and biopharmaceutical properties, out performing the reference profiles. CONCLUSIONS:New fast-dissolving pharmaceutical dosage forms of benznidazole were developed, which could improve the etiological treatment of the disease (especially in the pediatric field) and become a proper tool for its commercial exploitation
Subject(s)
Humans , Administration, Oral , Antiparasitic Agents/pharmacology , Antiparasitic Agents/therapeutic use , Tablets/pharmacology , Chagas Disease/therapy , Gels/pharmacologyABSTRACT
Descoberta há cem anos, a doença de Chagas afetaa mais de quinze milhões de pessoas em toda aAmérica Latina e, ainda hoje, não há tratamentoeficaz. O fármaco benznidazol, utilizado como únicaopção de tratamento no Brasil, é ineficaz na fasecrônica da doença. Problemas relacionados à biodisponibilidadedo medicamento comercial limitam suaeficácia, principalmente na fase crônica, quando osparasitos estão confinados em tecidos profundos eem lenta replicação. Nesse contexto, pesquisas lideradaspor grupos brasileiros e argentinos vêm sendoconduzidas com o objetivo de desenvolver formulaçõesde benznidazol mais eficientes. Diversas formasfarmacêuticas sólidas e líquidas foram propostas nosúltimos anos com resultados pré-clínicos promissores,sendo descritas melhorias acentuadas nas característicasfarmacocinéticas desse fármaco. Espera-seque as formas inovadoras apresentadas possam seravaliadas em ensaios clínicos e incorporadas à produçãoindustrial em breve.
Discovered about a hundred years ago, Chagas diseasecurrently affects more than fifteen million people in LatinAmerica, and it still remains without any effective treatment.Although benznidazole has been used as the onlypharmacotherapeutic option to treat Chagas disease inBrazil, it is ineffective in the chronic phase of the disease,when the parasites are confined to deep tissue layers andslowly replicate. This happens mainly due to problems related to the bioavailability of the drug, which is currentlyin the market. In this context, Brazilian and Argentineanresearch groups have conducted studies to develop moreefficient benznidazole formulations. Several solid andliquid formulations have been proposed over the last fewyears with promising preclinical results. Improvementsin the pharmacokinetic properties of this drug have beendescribed. Therefore, it is expected, that such innovative drugs and formulations be assessed in clinical trials andsoon incorporated to industrial production.