Effect of L-leucine on the electrostatic charging of inhalable salbutamol sulfate powder aerosols.

This study aimed to evaluate the impact of L-leucine (LL) on the electrostatic charge characteristics of the spray-dried particles of salbutamol sulfate (SS) containing 5-95 % LL (SS). The addition of LL significantly altered the net charge magnitude and polarity of composite powders, with a transition from positive to negative polarity occurring at 5 % LL. Maximum charging was observed between 5 and 30 % LL, followed by a reduction in charge and a return to positive polarity at LL contents ≥ 40 %, attributed to the progressive crystallinity of LL. X-ray diffraction confirmed LL's crystallization on the particle surface, which reduced charge accumulation and introduced a more consistent charging behaviour. The amorphous-to-crystalline transition influenced contact electrification, with amorphous powders exhibiting higher charge variability. Functional group analysis and surface composition from X-ray photoelectron spectroscopy revealed that LL's hydrophobic isobutyl side chain and hydrogen-bonding interactions between SS and LL modified charge dynamics and thermal properties, as supported by differential scanning calorimetry and thermogravimetric analysis data. Increased LL coverage on the particle surface increased corrugation, reduced contact area and influenced triboelectric charging. This work provides a foundation for further studies on the interplay between excipient properties and the electrostatic charge of pharmaceutical powder aerosols.