title: Looking for the interactions between omeprazole and amoxicillin in a disordered phase. An experimental and theoretical study.
abstract: 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.
authors.affiliation: Inorganic Chemistry, INTEQUI, National University of San Luis, Chacabuco and Pedernera-5700, San Luis, Argentina.
authors.forename: Marcos G
authors.initials: MG
authors.lastname: Russo
authors.affiliation: Physical Chemical Laboratory, National University of San Luis, Chacabuco and Pedernera-5700, San Luis, Argentina.
authors.forename: Matias I
authors.initials: MI
authors.lastname: Sancho
authors.affiliation: Chemistry Department, Federal University of São Carlos, PO Box 676, 13565-905 São Carlos, Brazil.
authors.forename: Lorena M A
authors.initials: LM
authors.lastname: Silva
authors.affiliation: Institute of Applied Mathematics San Luis (IMASL-CONICET), National University of San Luis, Chacabuco and Pedernera-5700, San Luis, Argentina.
authors.forename: Hector A
authors.initials: HA
authors.lastname: Baldoni
authors.affiliation: Chemistry Department, Federal University of São Carlos, PO Box 676, 13565-905 São Carlos, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Venancio
authors.affiliation: Physics Institute of São Carlos, University of São Paulo, CP 369, 13560-970 São Carlos, SP, Brazil.
authors.forename: Javier
authors.initials: J
authors.lastname: Ellena
authors.affiliation: Inorganic Chemistry, INTEQUI, National University of San Luis, Chacabuco and Pedernera-5700, San Luis, Argentina. Electronic address: gnarda@unsl.edu.ar.
authors.forename: Griselda E
authors.initials: GE
authors.lastname: Narda
mesh_terms: D000658:Amoxicillin / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D004347:Drug Interactions; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009853:Omeprazole / Q000737:chemistry* / Q000494:pharmacology; D033362:Powder Diffraction; D054328:Proton Pump Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011789:Quantum Theory; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D000658:Amoxicillin; D009853:Omeprazole
keywords: Amoxicillin; DFT; Disordered phases; Drugs interactions; FTIR; NBO; Omeprazole; QTAIM; ssNMR