In silico bioavailability for BCS class II efavirenz tablets using biorelevant dissolution media for IVIVR and simulation of formulation changes
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
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| Enthalten in: |
Drug development and industrial pharmacy - 47(2021), 8 vom: 08. Aug., Seite 1342-1352 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Silva, Thalita Martins da [VerfasserIn] |
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| Links: |
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| Themen: |
Alkynes |
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| Anmerkungen: |
Date Completed 26.04.2022 Date Revised 27.04.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/03639045.2021.1991368 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM331637243 |
|---|
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| 024 | 7 | |a 10.1080/03639045.2021.1991368 |2 doi | |
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| 041 | |a eng | ||
| 100 | 1 | |a Silva, Thalita Martins da |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a In silico bioavailability for BCS class II efavirenz tablets using biorelevant dissolution media for IVIVR and simulation of formulation changes |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 26.04.2022 | ||
| 500 | |a Date Revised 27.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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™ | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BCS class II | |
| 650 | 4 | |a Biorelevant dissolution media | |
| 650 | 4 | |a DDDPlus | |
| 650 | 4 | |a GastroPlus | |
| 650 | 4 | |a efavirenz | |
| 650 | 4 | |a in silico simulation | |
| 650 | 4 | |a in vitro–in vivo relationship | |
| 650 | 7 | |a Alkynes |2 NLM | |
| 650 | 7 | |a Benzoxazines |2 NLM | |
| 650 | 7 | |a Cyclopropanes |2 NLM | |
| 650 | 7 | |a Tablets |2 NLM | |
| 650 | 7 | |a efavirenz |2 NLM | |
| 650 | 7 | |a JE6H2O27P8 |2 NLM | |
| 700 | 1 | |a Honorio, Thiago da Silva |e verfasserin |4 aut | |
| 700 | 1 | |a Chaves, Marcelo Henrique da Cunha |e verfasserin |4 aut | |
| 700 | 1 | |a Duque, Marcelo Dutra |e verfasserin |4 aut | |
| 700 | 1 | |a Cabral, Lucio Mendes |e verfasserin |4 aut | |
| 700 | 1 | |a Patricio, Beatriz Ferreira de Carvalho |e verfasserin |4 aut | |
| 700 | 1 | |a Rocha, Helvécio Vinícius Antunes |e verfasserin |4 aut | |
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