In silico bioavailability for BCS class II efavirenz tablets using biorelevant dissolution media for IVIVR and simulation of formulation changes.

Autor: Silva TMD; Farmanguinhos, Laboratório de Micro e Nanotecnologia, Rio de Janeiro, Brasil.; Pesquisa e Desenvolvimento na Indústria Farmacêutica, Farmanguinhos, Programa de Pós-graduação Profissional em Gestão, Rio de Janeiro, Brazil., Honorio TDS; Laboratório de Tecnologia Industrial Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Chaves MHDC; Farmanguinhos, Laboratório de Micro e Nanotecnologia, Rio de Janeiro, Brasil., Duque MD; Laboratório de Farmacotécnica e Cosmetologia, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, Brazil., Cabral LM; Laboratório de Tecnologia Industrial Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Patricio BFC; Farmanguinhos, Laboratório de Micro e Nanotecnologia, Rio de Janeiro, Brasil., Rocha HVA; Farmanguinhos, Laboratório de Micro e Nanotecnologia, Rio de Janeiro, Brasil.; Pesquisa e Desenvolvimento na Indústria Farmacêutica, Farmanguinhos, Programa de Pós-graduação Profissional em Gestão, Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Drug development and industrial pharmacy [Drug Dev Ind Pharm] 2021 Aug; Vol. 47 (8), pp. 1342-1352. Date of Electronic Publication: 2021 Oct 21.
DOI: 10.1080/03639045.2021.1991368
Abstrakt: 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.
Databáze: MEDLINE
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