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In silico bioavailability for BCS class II efavirenz tablets using biorelevant dissolution media for IVIVR and simulation of formulation changes.
Silva, Thalita Martins da; Honorio, Thiago da Silva; Chaves, Marcelo Henrique da Cunha; Duque, Marcelo Dutra; Cabral, Lucio Mendes; Patricio, Beatriz Ferreira de Carvalho; Rocha, Helvécio Vinícius Antunes.
Afiliação
  • Silva TMD; Farmanguinhos, Laboratório de Micro e Nanotecnologia, Rio de Janeiro, Brasil.
  • Honorio TDS; Pesquisa e Desenvolvimento na Indústria Farmacêutica, Farmanguinhos, Programa de Pós-graduação Profissional em Gestão, Rio de Janeiro, Brazil.
  • Chaves MHDC; Laboratório de Tecnologia Industrial Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Duque MD; Farmanguinhos, Laboratório de Micro e Nanotecnologia, Rio de Janeiro, Brasil.
  • Cabral LM; Laboratório de Farmacotécnica e Cosmetologia, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, Brazil.
  • Patricio BFC; Laboratório de Tecnologia Industrial Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Rocha HVA; Farmanguinhos, Laboratório de Micro e Nanotecnologia, Rio de Janeiro, Brasil.
Drug Dev Ind Pharm ; 47(8): 1342-1352, 2021 Aug.
Article em En | MEDLINE | ID: mdl-34622730
OBJECTIVE: This work aims to evaluate the ability of biorelevant dissolution media to simulate the bioavailability of efavirenz tablets, establish an in vitro-in vivo relationship (IVIVR) based on in vivo data using GastroPlus® and simulate formulation changes using DDDPlus™. METHODS: Solubility and drug release profiles were conducted in SLS 0.5% and biorelevant media, such as FaSSIF, FeSSIF, FaSSIF-V2, and FeSSIF-V2. The efavirenz physicochemical properties were used to simulate the plasma concentration profile and compare the simulated pharmacokinetic parameters in fasted and fed states. An IVIVR was developed using Loo-Riegelman as the deconvolution method to estimate drug bioavailability. DDDPlus™ was used to perform virtual trials of formulations to evaluate whether formulations changes and the efavirenz particle size could influence the bioavailability. RESULTS: The drug dissolution displayed higher levels in the biorelevant media that simulated gut-fed state (FeSSIF and FeSSIF-V2). The absorption model successfully predicted the efavirenz pharmacokinetics, and FeSSIF-V2 was chosen as the predictive dissolution media, while an IVIVR was established using the Loo-Riegelman deconvolution method. CONCLUSIONS: The present work provides valuable information about efavirenz solubility and kinetics in the gastrointestinal tract, allowing an IVIVR to support future formulation changes. This understanding is essential for rational science-driven formulation development. At least, this study also showed the validity and applicability of in vitro and in silico tools in the regulatory scenario helping on drug development.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Modelos Biológicos Tipo de estudo: Prognostic_studies Idioma: En Revista: Drug Dev Ind Pharm Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Modelos Biológicos Tipo de estudo: Prognostic_studies Idioma: En Revista: Drug Dev Ind Pharm Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido