Can we predict trends in tribo-charging of pharmaceutical materials from first principles?

Tribo-charging can negatively impact safety and efficacy of pharmaceutical products due to particle agglomeration and adherence to surfaces resulting in poor mixing and inaccurate dosing. Prediction of relative charging trends in-silico and from first principles could provide an efficient tool for guiding development during early formulation studies. We experimentally investigate tribo-charging of pharmaceutical compounds and compare the results with energies from electronic-structure-calculations. Calculations were performed applying different levels of theory (semi-empirical and DFT with different functionals) to estimate properties including ionization potentials (IP), and work functions (WF). The calculations are performed for single molecules assuming that, at least, relative properties of the solid phase are reproduced. Our results suggest that, independently of the level of theory, calculated IP values correlate well with experimental tribo-charging trends provided we use the adiabatic IP. By comparison, WF values, calculated by a commonly used approximation, turn out being a poor descriptor for tribo-charging trends.