Physical Stability of Ibuprofen Upon Co-Milling with Caffeine and Polyvinylpyrrolidone at Room Temperature

Abstract

The purpose of this work is to investigate the physical stability of a ternary amorphous system (Ibuprofen, Caffeine, Polyvinylpyrrolidone (PVP K30)) generated by co-milling technique at room temperature, as well as the intermolecular interactions that could contribute to physical stabilization of amorphous ibuprofen (a poorly water-soluble drug). The milled mixtures were characterized by x-ray diffraction (XRD), infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electronic microscopy (SEM). As shown by XRD results, amorphous Ibuprofen maintains its physical stability even after exposure to high humidity levels (RH = 75%, T = 40°C) for 6 months. FTIR results highlighted the establishment of hydrogen bonds in the binary and ternary systems involving the carboxylic group of Ibuprofen. At higher amounts (more than 75%), the polyvinylpyrrolidone has totally amorphized drug/caffeine mixtures and inhibited polymorphic transition of Caffeine (Form II ≥ Form I) which occurred at higher temperatures. Thus, this polymer has shown an ability to stabilize amorphous solid dispersion (Ibuprofen: Caffeine) and preserve the chemical structure of each molecule.