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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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