Electrostatic charge of pharmaceutical aerosols

Abstract

Electrostatic charging plays a critical yet poorly understood role in the performance of inhalation aerosols by influencing particle adhesion, dispersion, and lung deposition. This thesis investigates the mechanisms governing electrostatic charge in pharmaceutical aerosol systems, with particular emphasis on the roles of surface chemistry, excipients, and environmental humidity. A foundational review of dry powder inhalers (DPIs) identifies key gaps in understanding molecular-level charge transfer, the interplay between surface composition and humidity, and limitations in charge measurement reproducibility. Experimental studies on pressurised metered dose inhalers (pMDIs) demonstrate that propellant physicochemical properties strongly influence electrostatic behaviour, with HFA-152a generating higher and bipolar charge distributions compared to HFA-134a, while the effect of tetraethylsilane is shown to be propellant-dependent. The influence of L-leucine (LL) as a surface-active excipient is systematically evaluated in spray-dried salbutamol sulfate (SS) and disodium cromoglycate (DSCG) powders, where LL modulates charge magnitude and polarity, with peak charging at intermediate concentrations and more stable, reduced charging at higher LL content due to increased crystallinity. Surface characterisation reveals that LL alters particle morphology, reduces contact area, and modifies triboelectric interactions, with distinct behaviours observed between SS and DSCG due to differences in hygroscopicity and drug–excipient interactions. Furthermore, under varying relative humidity (15–85%), LL stabilises electrostatic charge in SS formulations but not in DSCG systems, highlighting formulation-dependent effects. Overall, this work provides mechanistic insights to support the rational design of more robust inhalation formulations.