Free-Base Nicotine Fraction α_fb in Non-Aqueous versus Aqueous Solutions: Electronic Cigarette Fluids Without versus...

An important design aspect of electronic cigarettes ("e-cigarettes") is the nature of the acid/base chemistry in the e-liquid phase. E-liquids having formulations similar to those of early products are mixes of propylene glycol/glycerol (PG/GL) plus free-base (fb) nicotine and (usually) flavor chemicals that are either rather weak or non-acid/base actors in PG/GL. The fraction of nicotine in the fb form is denoted (α_fb)_e-liquid, with a possible range of 0 < (α_fb)_e-liquid < 1. For e-liquids of an early design, (α_fb)_e-liquid ≈ 1. Because e-cigarette aerosols high in fb nicotine are harsh upon inhalation, many commercial e-liquids now also contain variable levels of an acid additive (e.g., benzoic acid, levulinic acid, etc.) to protonate the nicotine and form dissolved "nicotine salts": (α_fb)_e-liquid values significantly less than 1 are now common. A framework is developed for predicting α_fb values in a given medium based on the following: (1) acid/nicotine ratios and (2) overall acid + nicotine protonation constant (K_oa) values. This framework is required for understanding (1) e-liquid design in regard to how acid additives affect (α_fb)_e-liquid values, and (2) why (α_fb)_e-liquid values cannot, in general, be measured by any method that involves significant dilution with water.