Mechanochemical synthesis of drug–drug eutectics of the antibacterial agent, linezolid

Abstract

The antibacterial drug linezolid (LZD) has only a limited number of multicomponent systems known in the literature, though it has an optimal number and distribution of potential hydrogen bond forming functionalities. We used complementary experimental and computational methods to screen for the multicomponent systems of LZD with other drug compounds. Adopting mechanochemical synthetic pathways, we attempted twelve combinations; seven formed drug–drug eutectics, while the rest remained physical mixtures. The pure eutectic compositions for all seven composites were estimated by combining hot stage microscopy (HSM) and differential scanning calorimetry (DSC) data. The heterogeneous crystalline arrangements in eutectics with weak interphase interactions contribute to their high thermodynamic functions, such as free energy, enthalpy, and entropy, thus demonstrating their characteristic solubility/dissolution advantages. Mechanochemical synthesis of drug–drug eutectics offers promising applications in the creation of drug–drug eutectics with increased manufacturability without altering crystallinity or causing chemical disintegration.