Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/50646
Type: Artigo de Periódico
Title: Polymorphic and quantum chemistry characterization of candesartan cilexetil: importance for the correct drug classification according to biopharmaceutics classification system
Authors: Débora Priscila de Campos
Neila Márcia Silva Barcellos
Renata Rodrigues Lima
Ranylson Marcello Leal Savedra
Melissa Fabíola Siqueira
Maria Irene Yoshida
Wagner da Nova Mussel
Jacqueline de Souza
Abstract: The recommended method for the biopharmaceutical evaluation of drug solubility is the shake flask; however, there are discrepancies reported about the solubility of certain compounds measured with this method, one of them is candesartan cilexetil. The present work aimed to elucidate the solubility of candesartan cilexetil by associating others assays such as stability determination, polymorphic characterization and in silico calculations of intrinsic solubility, ionized species, and electronic structures using quantum chemistry descriptors (frontier molecular orbitals and Fukui functions). For the complete biopharmaceutical classification, we also reviewed the permeability data available. The polymorphic form used was previously identified as the form I of candesartan cilexetil. The solubility was evaluated in biorelevant media in the pH range of 1.2–6.8 at 37.0°C according to the stability previously assessed. The solubility of candesartan cilexetil is pH dependent and the dose/solubility ratios obtained demonstrated the low solubility of the prodrug. The in silico calculations supported the found results and evidenced the main groups involved in the solvation, benzimidazole, and tetrazol-biphenyl. The human absolute bioavailability reported demonstrates that candesartan cilexetil has low permeability and when associated with the low solubility allows to classify it as class 4 of the Biopharmaceutics Classification System.
Subject: Química quântica
Físico-química
Polimorfismo (Cristalografia)
Solubilidade
Permeabilidade
Medicamentos - Estabilidade
Agentes hipotensores
Biofarmacêutica
Fármacos - Classificação
Solvação
Orbitais moleculares
Análise térmica
Raios X - Difração
language: eng
metadata.dc.publisher.country: Brasil
Publisher: Universidade Federal de Minas Gerais
Publisher Initials: UFMG
metadata.dc.publisher.department: ICX - DEPARTAMENTO DE QUÍMICA
Rights: Acesso Restrito
metadata.dc.identifier.doi: https://doi.org/10.1208/s12249-018-1129-6
URI: http://hdl.handle.net/1843/50646
Issue Date: Oct-2018
metadata.dc.url.externa: https://link.springer.com/article/10.1208/s12249-018-1129-6
Appears in Collections:Artigo de Periódico

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