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

Author(s)

Russo, Marcos G. ^{[1, 2]} ; Sancho, Matias I. ^{[3, 4]} ; Silva, Lorena M. A. ^[5] ; Baldoni, Hector A. ^{[6, 7]} ; Venancio, Tiago ^[5] ; Ellena, Javier ^[8] ; Narda, Griselda E. ^{[1, 2]}

Affiliation

^[1] Natl Univ San Luis, INTEQUI, Inorgan Chem, RA-5700 Chacabuco, San Luis - Argentina

^[2] Natl Univ San Luis, INTEQUI, Inorgan Chem, RA-5700 Pedernera, San Luis - Argentina

^[3] Natl Univ San Luis, Phys Chem Lab, RA-5700 Chacabuco, San Luis - Argentina

^[4] Natl Univ San Luis, Phys Chem Lab, RA-5700 Pedernera, San Luis - Argentina

^[5] Univ Fed Sao Carlos, Dept Chem, POB 676, BR-13565905 Sao Carlos, SP - Brazil

^[6] Natl Univ San Luis, Inst Appl Math San Luis IMASL CONICET, RA-5700 Chacabuco, San Luis - Argentina

^[7] Natl Univ San Luis, Inst Appl Math San Luis IMASL CONICET, RA-5700 Pedernera, San Luis - Argentina

^[8] Univ Sao Paulo, Phys Inst Sao Carlos, CP 369, BR-13560970 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY; v. 156, p. 70-77, MAR 5 2016.
• Web of Science Citations: 5

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. (c) 2015 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 09/13860-2 - Application of solid state nuclear magnetic resonance and chemometric tools to the characterization of polimorphism in drugs
• Grantee: Tiago Venancio
• Support Opportunities: Regular Research Grants