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Use of In silico Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach.
da Silva Honório, Thiago; Simon, Alice; Machado, Raiane Monteiro Clacino; Rodrigues, Carlos Rangel; do Carmo, Flávia Almada; Cabral, Lucio Mendes; de Sousa, Valeria Pereira.
Afiliação
  • da Silva Honório T; Laboratory of Molecular Modeling & QSAR, Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Simon A; Laboratory of Cell Culture (LabCel), Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Machado RMC; Laboratory of Cell Culture (LabCel), Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Rodrigues CR; Laboratory of Pharmaceutical Industrial Technology (LabTIF), Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • do Carmo FA; Laboratory of Pharmaceutical Industrial Technology (LabTIF), Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Cabral LM; Laboratory of Molecular Modeling & QSAR, Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • de Sousa VP; Laboratory of Pharmaceutical Industrial Technology (LabTIF), Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Curr Pharm Des ; 29(38): 3040-3049, 2023.
Article em En | MEDLINE | ID: mdl-37957861
BACKGROUND: Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability. OBJECTIVE: The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems. METHODS: Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied. Previously, solid-state structure and particle size in active pharmaceutical ingredients were characterized and the impact of differences on solubility was evaluated for the choice of discriminative medium. Afterwards, particle size distribution (0.1 to 360 µm), dissolution profile, and in vitro permeability in Caco-2 cell of commercial suspensions, were determined. These parameters were used as input for the establishment of the in vitro-in vivo correlation (IVIVC) for the suspensions using the GastroPlus™ with Wagner-Nelson and Loo- Riegelmann deconvolution approach. RESULTS: The predicted/observed pharmacokinetic model showed good correlation coefficients (r) of 0.960, 0.950, and 0.901, respectively. The IVIVC was established for one nimesulide and two ibuprofen suspensions with r between 0.956 and 0.932, and the percent prediction error (%PE) did not exceed 15%. CONCLUSION: In this work, we have performed a complete study combining in vitro/in silico approaches with the aim of anticipating the safety and efficacy of oral pharmaceutical suspensions in order to provide a regulatory tool for this category of products in a faster and more economical way.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sulfonamidas / Ibuprofeno Limite: Humans Idioma: En Revista: Curr Pharm Des Assunto da revista: FARMACIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Emirados Árabes Unidos
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: Sulfonamidas / Ibuprofeno Limite: Humans Idioma: En Revista: Curr Pharm Des Assunto da revista: FARMACIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Emirados Árabes Unidos