Triboelectric Charging Properties of the Functional Groups of Common Pharmaceutical Materials Using Density Functional Theory Calculations.

Triboelectrification is a ubiquitous and poorly understood phenomenon in powder processing, particularly for pharmaceutical powders. Charged particles can adhere to vessel walls, causing sheeting; they can also cause agglomeration, threatening the stability of powder formulations, and in extreme cases electrostatic discharges, which present a serious fire and explosion hazard. Triboelectrification is highly sensitive to environmental and material conditions, which makes it very difficult to compare experimental results from different publications. In this work, density functional theory (DFT) is used to investigate the charge transfer characteristics of several functional groups of paracetamol in order to better understand the mechanisms of charging at the nanoscale and the influence of the environmental and material properties on charge transfer. This is achieved by studying the structure and electronic properties at the molecule-substrate interface. Using this molecule-substrate approach, the charging contributions of individual functional groups are explored by examining the Hirschfeld charges, the charge density difference between the molecule and substrate, the density of states, and the location of the frontier orbitals (HOMO and LUMO) of a paracetamol molecule. Charge density difference calculations indicate a significant transfer of charge from the molecule to the surface. Observable regions of electron density enrichment and depletion are evident around the electron-donating and -withdrawing groups, respectively. The density of states for the paracetamol molecule evolves as it approaches the surface, and the band gap disappears upon contact with the substrate. Hirshfeld charge analysis reveals asymmetry in the charge redistribution around the molecule, highlighting the varying charging tendencies of different atoms.

Prediction of the Effective Work Function of Aspirin and Paracetamol Crystals by Density Functional Theory-A First-Principles Study.

Crystals of active pharmaceutical ingredients (API) are prone to triboelectric charging due to their dielectric nature. This characteristic, coupled with their typically low density and often large aspect ratio, poses significant challenges in the manufacturing process. The pharmaceutical industry frequently encounters issues during the secondary processing of APIs, such as particle adhesion to walls, clump formation, unreliable flow, and the need for careful handling to mitigate the risk of fire and explosions. These challenges are further intensified by the limited availability of powder quantities for testing, particularly in the early stages of drug development. Therefore, it is highly desirable to develop predictive tools that can assess the triboelectric propensity of APIs. In this study, Density Functional Theory calculations are employed to predict the effective work function of different facets of aspirin and paracetamol crystals, both in a vacuum and in the presence of water molecules on their surfaces. The calculations reveal significant variations in the work function across different facets and materials. Moreover, the adsorption of water molecules induces a shift in the work function. These findings underscore the considerable impact of distinct surface terminations and the presence of molecular water on the calculated effective work function of pharmaceuticals. Consequently, this approach offers a valuable predictive tool for determining the triboelectric propensity of APIs.