Rational Design of a Famotidine-Ibuprofen Co-amorphous System: An Experimental and Theoretical Study

Y. DAVILA; G. E. NARDA; M. G. RUSSO; E. V. BRUSAU; H. A. BALDONI; J. A. ELLENA

JOURNAL OF PHYSICAL CHEMISTRY B - (Print)

AMER CHEMICAL SOC

Lugar: Washington; Año: 2018 vol. 122 p. 8772 - 8782

1520-6106

Famotidine (FMT) and ibuprofen (IBU) were used as model drugs to obtain co-amorphoussystems, where the guanidine moiety of the antacid and the carboxylic group of the NSAID,could potentially participate in H-bonds leading to a given structural motif. The systemswere prepared in 3:7, 1:1 and 7:3 FMT and IBU molar ratios, respectively. The latter twobecame amorphous after 180 minutes of co-milling. 1:1 FMT-IBU exhibited a higherphysical stability in assays at 4, 25 and 40 °C up to 60 days. FTIR spectroscopy accountedfor important modifications in the vibrational behavior of those functional groups, allowingto ascribe the skill of 1:1 FMT-IBU for remaining amorphous to equimolar interactionsbetween both components. DFT calculations followed by QTAIM analysis were thenconducted to support the presence of the expected FMT-IBU heterodimer withconsequently formation of a 8 structural motif. The electron density (ρ) and its Laplacian(∇2ρ) values suggested a high strength of the specific intermolecular interactions.Molecular Dynamics simulations to build an amorphous assembly, followed by RDFanalysis on the modeled phase were further employed. The results demonstrate that isfeasible a rational design of a co-amorphous system, satisfactorily stabilized by molecularlevelinteractions leading to the expected motif.