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In Vivo and In Vitro Taste Assessment of Artesunate-Mefloquine, Praziquantel, and Benznidazole Drugs for Neglected Tropical Diseases and Pediatric Patients

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Abstract

The assessment of drug taste is crucial for pediatric treatments so that formulations can be developed to enhance their effectiveness. In this study, in vivo and in vitro methods were applied to evaluate the taste of tablets of three drugs administered to children without taste-masking excipients to treat tropical diseases, namely artesunate-mefloquine (ASMQ), praziquantel (PZQ), and benznidazole (BNZ). In the first method, a model of rat palatability was adapted with recirculation to ensure sample dispersion, and the data were analyzed using ANOVA (single factor, 95%). The taste assessment results (in vivo) indicated an aversion to the three medicines, denoted by the animals retracting themselves to the bottom of the box after the first contact with the drugs. For the placebo samples, the animals behaved normally, indicating that taste perception was acceptable. The second method was based on the in vitro analysis of capacitance data from a homemade impedimetric electronic tongue. Consistent with the in vivo taste assessment results, the data points obtained with PZQ, ASMQ, and BNZ were far away from those of their placebos in a map built with the multidimensional projection technique referred to as Interactive Document Mapping (IDMAP). A combined analysis of the results with the two methods allowed us to confirm the bitterness of the three drugs, also pointing to electronic tongues as a promising tool to replace in vivo palatability tests.

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Acknowledgements

The authors are grateful for the financial support by PAPES VII, PROEP/FAR/CNPq/Fiocruz, CNPQ, and FAPESP (2018/22214-6). Also, we would like to thank Luciano Simoes Pereira for all support with the image treatment and the recirculation system construction. The authors also thank Angelo L. Gobbi and Maria H. O. Piazzetta for their technical assistance in the microfabrication laboratory (LMF/LNNano/CNPEM).

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Authors and Affiliations

  1. Oswaldo Cruz Foundation, Sizenando Nabuco Street, 100, Rio de Janeiro, RJ, Brazil

    Janine Boniatti, Marcelo R. R. Tappin, Tamires de A V Gandos, Laís B. da Fonseca, Fabio C. Amendoeira & Alessandra L. Viçosa

  2. Faculty of Pharmacy, Federal Fluminense University, Niterói, RJ, Brazil

    Rafaela G. da S Teixeira, Tamires de A V Gandos, Luis P. S. Rios, Izabelle A. M. Ferreira, Karina C. Oliveira & Sabrina Calil-Elias

  3. Pharmaceutical Laboratory in the State of Pernambuco – Lafepe, Recife, PE, Brazil

    Aila K. M. Santana

  4. Department of Applied Physics, “Gleb Wataghin” Institute of Physics (IFGW), University of Campinas (UNICAMP), Campinas, SP, 13083-859, Brazil

    Flavio M. Shimizu

  5. São Carlos Institute of Physics, University of São Paulo, P.O. Box 369, São Carlos, SP, 13560-970, Brazil

    Olívia Carr & Osvaldo N. Oliveira Jr

  6. Material Department, National Institute of Technology, Rio de Janeiro, RJ, Brazil

    Janine Boniatti & Fabio M. L. Dantas

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  1. Janine Boniatti
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Contributions

Conceptualization: J.B., A.L.V., R.G.S.T., S.C.E.

Experimental procedure: J.B., R.G.S.T., L.P.S.R., I.A.M.F., T.A.V.G., O. C., A.K.M.S., K.C.O

Data curation: J.B., R.G.S.T., F.M.S., M.R.R.T.

Writing-original draft preparation: J.B., F.M.S., M.R.R.T.

Review and editing: J.B., F.M.S., A.L.V, L.B.d.F., O.N.O. Jr., S.C.E.,

Review: F.M.L.D., F.C.A

Supervision: A.L.V, S.C.E, O.N.O. Jr.

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Correspondence to Janine Boniatti.

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This article was updated to correct Tables 1 and 2.

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Boniatti, J., Tappin, M.R.R., da S Teixeira, R.G. et al. In Vivo and In Vitro Taste Assessment of Artesunate-Mefloquine, Praziquantel, and Benznidazole Drugs for Neglected Tropical Diseases and Pediatric Patients. AAPS PharmSciTech 23, 22 (2022). https://doi.org/10.1208/s12249-021-02162-z

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