Interfacial modulation of alkaloid release pathways in aqueous-polyol solvents: Protonation-dependent vaporization kinetics

The release efficiency of alkaloids (e.g. nicotine) in aerosol-generating systems is strongly influenced by solvent-mediated molecular interactions at interfaces. Here, we demonstrate that glycerol, as a polyol co-solvent, shifts the protonation equilibrium of nicotine in aqueous solutions, thereby regulating its vaporization pathways. Through thermo-gravimetric analysis coupled with mass spectrometry (TGA-MS), we reveal that glycerol elevates the boiling point of aqueous-polyol systems (>130 °C at water fraction of 0.35), enabling nicotine release via non-protonated (110–130 °C) and mono-protonated (130–170 °C) forms — a 100% increase in low-temperature release efficiency compared to polyol-free systems. Kinetic analysis shows glycerol increases the apparent activation energy of nicotine release from 50.5 kJ/mol to 73.5 kJ/mol, while boosting the pre-exponential factor by 4 orders of magnitude. This kinetic compensation effect suggests that although glycerol introduces a higher energy barrier for desorption, it also creates a more favorable interfacial configuration for release. Spectroscopic evidence further confirms that glycerol stabilizes mono-protonated nicotine in acidic solution (pH 5.0), whereas ethanol promotes the di-protonated form. This strategy of interfacial protonation regulation offers a useful perspective for designing colloid-stable aerosol delivery systems. • Glycerol actively modulates nicotine release by shifting its protonation state and forming a high-boiling-point system. • This modulation enables a 50% increase in nicotine release efficiency at lower temperatures (110–130 °C). • The enhanced release stems from increased molecular mobility at the interface, boosting the pre-exponential factor. • This work demonstrates the importance of interfacial protonation control for designing efficient aerosol delivery systems.