Development of benznidazole orally disintegrating tablets for paediatric patients.

Objectives: To develop the orphan drug benznidazole (BNZ) in orally disintegrating tablets, for the neglected disease American Trypanosomiasis (Chagas disease) therapy. Although children are highly affected by this disease, there are no specific commercial pharmaceutical preparations for this age group in Argentina and in many other countries.

Methods: In the production process, co-milling in a ball mill was applied to enhance dissolution rates, followed by direct compression. Taste preference and taste masking experiments were conducted in a test panel of adult volunteers. The tablets were fully characterized and their stability and bioavailability determined.

Key findings: The tablets complied with all the quality control prerequisites, their disintegration time was 30 s, and as a consequence of the intimate mixture with hydrophilic excipients and particle size reduction, BNZ dissolution was improved, reaching 75% in 0.1 N hydrochloric acid and 62% in simulated salivary fluid, after 5 min. X-ray diffraction studies showed that BNZ maintained its original crystalline state (form I) in the tablets. The ODTs remained stable for at least 1 year. Oral bioavailability of BNZ of suspensions obtained from the prepared ODTs was comparable with that of pulverized commercial tablets.

Conclusions: The developed tablets may improve paediatric Chagas disease therapeutics.