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Leonardo Henrique Toehwé
1Programa de Pós-graduação Profissional em Gestão, Pesquisa e Desenvolvimento na Indústria Farmacêutica – Farmanguinhos – Fiocruz – Rio de Janeiro – RJ – Brazil
Brasil
Thiago da Silva Honorio
Laboratório de Tecnologia Industrial Farmacêutica, Departamento de Fármacos e Medicamentos - Faculdade de Farmácia - Universidade Federal do Rio de Janeiro - Rio de Janeiro – RJ – Brazil.
Brasil
https://orcid.org/0000-0002-3772-7225
Luiz Claudio Rodrigues Pereira da Silva
Laboratório de Nanoteranósticos, Departamento de Fármacos e Medicamentos - Faculdade de Farmácia – Universidade Federal do Rio de Janeiro - Rio de Janeiro – RJ – Brazil.
Brasil
https://orcid.org/0000-0002-6746-5756
Thalita Martins da Silva
Oswaldo Cruz Foundation
Brasil
https://orcid.org/0000-0001-7685-3120
Luciana da Rocha Pitta
Laboratório de Micro e Nanotecnologia – Farmanguinhos – Fiocruz – Rio de Janeiro – RJ – Brazil.
Brasil
https://orcid.org/0000-0002-2652-4182
Livia Deris Prado
Laboratório de Micro e Nanotecnologia – Farmanguinhos – Fiocruz – Rio de Janeiro – RJ – Brazil.
Brasil
https://orcid.org/0000-0002-5691-9900
Lucio Mendes Cabral
Laboratório de Tecnologia Industrial Farmacêutica, Departamento de Fármacos e Medicamentos - Faculdade de Farmácia - Universidade Federal do Rio de Janeiro - Rio de Janeiro – RJ – Brazil.
Brasil
Helvécio Vinícius Antunes Rocha
Programa de Pós-graduação Profissional em Gestão, Pesquisa e Desenvolvimento na Indústria Farmacêutica – Farmanguinhos – Fiocruz – Rio de Janeiro – RJ – Brazil.; Laboratório de Micro e Nanotecnologia – Farmanguinhos – Fiocruz – Rio de Janeiro – RJ – Brazil.
Brasil
https://orcid.org/0000-0002-9624-6405
Vol. 62 Núm. 4 (2021), Artículos Originales, Páginas 358-370
DOI: https://doi.org/10.30827/ars.v62i4.21029
Recibido: abr 19, 2021 Aceptado: sep 5, 2021 Publicado: sep 20, 2021
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Resumen

Introduction: The immediate-release solid oral products containing very soluble and permeable drugs are candidates for the biowaiver process. This work aims to compare in vitro, in silico, and in vivo data to establish if previously published prednisone oral tablet formulations are biowaiver candidates.


Method: To achieve this goal, permeation studies were conducted on Caco-2 cells. A previous bioequivalence study between the test and the reference drug product was applied on an in silico evaluation using Gastroplus® to assess the bioequivalence of two other previously proposed formulations.


Results: The apparent permeability coefficient for prednisone presented a value of 3.69 x 10-5 cm/s in 180 minutes. The bioequivalence study shows that the tested and reference product was equivalent. The in silico simulations successfully predicted the pharmacokinetics of the tested and the other two formulations since they were validated with the in vivo study. Both exhibit the same plasma concentration vs. time profiles.


Conclusions: Through the in silico results, it is possible to infer that the other two formulations tested may be bioequivalent concerning the reference product. This result may be helpful in biowaiver requesting. Toward to reduce costs and the use of human beings in bioequivalence studies, this approach could be an essential way to work in the pharmaceutical industry.

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