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

• Omeprazole and anhydrous amoxicillin were obtaining as disordered phase.
• FTIR and ssNMR spectroscopy strongly suggest intermolecular interactions.
• B3LYP and MPW1B95 functional were employed to optimize the proposed heterodimers.
• QTAIM and NBO analyses were performed to analyze the intermolecular interactions.

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.

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