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

M. G. RUSSO; M.I.SANCHO; L.M.A.SILVA; H. BALDONI; T. VENANCIO; J. ELLENA; G.E. NARDA

SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY.

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016 vol. 156 p. 70 - 77

1386-1425

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 theaim of obtaining a co-amorphous system and determining the potential intermolecular interactions. Thesesystems 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 obtainingthe 1:1 CGMa disordered phase. Moreover, in this system both FTIR and ssNMR analysis strongly suggest intermolecularinteractions 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 theco-grinding process. Complementarily, we carried out density functional theory calculations (DFT) followed byquantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in order to shedsome light on the principles that guide the possible formation of heterodimers at the molecular level, whichare supported by spectroscopic experimental findings