Looking for the interactions between omeprazole and amoxicillin in a disordered phase. An experimental and theoretical study

In this paper, co-grinding mixtures of omeprazole-amoxicillin trihydrate (CGM samples) and omeprazole-anhydrous amoxicillin (CGMa samples) at 3:7, 1:1 and 7:3 molar ratios, respectively, were studied with the aim of obtaining a co-amorphous system and determining the potential intermolecular interac...

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Detalles Bibliográficos
Autores: Russo, Marcos Guillermo, Sancho, Matias Israel, Silva, Lorena M. A., Baldoni, Hector Armando, Venancio, Tiago, Ellena, Javier, Narda, Griselda Edith
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/60661
Acceso en línea:http://hdl.handle.net/11336/60661
Access Level:acceso abierto
Palabra clave:AMOXICILLIN
DFT
DISORDERED PHASES
DRUGS INTERACTIONS
FTIR
NBO
OMEPRAZOLE
QTAIM
SSNMR
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descripción
Sumario:In this paper, co-grinding mixtures of omeprazole-amoxicillin trihydrate (CGM samples) and omeprazole-anhydrous amoxicillin (CGMa samples) at 3:7, 1:1 and 7:3 molar ratios, respectively, were studied with the aim of obtaining a co-amorphous system and determining the potential intermolecular interactions. These systems were fully characterized by differential scanning calorimetry (DSC), FT-infrared spectroscopy (FTIR), X-ray powder diffraction (PXRD), scanning electron microscopy (SEM) and solid state Nuclear Magnetic Resonance (ssNMR). The co-grinding process was not useful to get a co-amorphous system but it led to obtaining the 1:1 CGMa disordered phase. Moreover, in this system both FTIR and ssNMR analysis strongly suggest intermolecular interactions between the sulfoxide group of omeprazole and the primary amine of amoxicillin anhydrous. The solubility measurements were performed in simulated gastric fluid (SGF) to prove the effect of the co-grinding process. Complementarily, we carried out density functional theory calculations (DFT) followed by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in order to shed some light on the principles that guide the possible formation of heterodimers at the molecular level, which are supported by spectroscopic experimental findings.