Phase separation and intermolecular binding energy of ibuprofen in some organic solvents

Abstract

The capacity of water-insoluble drug solution to endure its phase inversion influenced by water induction, water tolerance, was measured by using the titration method. The water tolerance of ibuprofen (IBU) solutions using ethanol, dimethyl sulfoxide, and N-methyl-2-pyrrolidone as the solvents was investigated for understanding their phase separation behaviors. The IBU solutions were titrated with distilled water and found that the water tolerance was affected with the content of IBU, type of solvent, and system temperature. Namely, IBU in ethanol (IE) solution showed a higher water tolerance than IBU in NMP solution (IN) and IBU in DMSO (ID). The water tolerance value of these IBU solutions at 37 °C was notably higher than that at room temperature. The phase separation rate of ID was higher than IN and IE, respectively. Thereafter, the H-bonding interactions and the binding energy between IBU and these organic solvents were investigated using density-functional theory (DFT) calculations. The binding energy between solvent in IE was apparently lower than those of IN and ID, respectively, indicated that solvent–solvent bonding could influence the water tolerance of the IBU solution. The relationship between phase separation property and binding energy provides the useful information for further development IBU solution as the in situ forming system with aqueous sensitive-induced phase transition mechanism which the solution phase changes itself into solid/semi-solid state for controlled drug release.