Abstract: E-Liquids are commonly made with free-base nicotine or protonated nicotine in various salts. Salt forms are perceived as less harsh by vapers. A crossover in-patient clinical study was performed to evaluate the impact of the nicotine form on plasma levels. Subjects vaped different nicotine strengths (3 – 50 mg/ml) of the same E-Liquid flavor (Tobacco Gold No. 1) made with either free-base nicotine or nicotine protonated with lactic acid (nicotine lactate). A total of 36 subjects vaped the products under controlled conditions: a 2-3 second puff every 30 seconds for a total of 10 puffs. The subjects also smoked their own brand cigarettes or chewed nicotine gum in an in-patient facility. Blood samples were drawn at time zero up to 180 minutes. Own-brand cigarette nicotine plasma levels peaked in 6 minutes with a maximum concentration of 18.7 ng/mL. The 35 and 50 mg/mL Tobacco Gold nicotine lactate E-Liquid peaked at 6 and 7 minutes at maximum concentrations of 14.6 and 16.2 ng/mL, respectively. The Tobacco Gold nicotine free base 18 mg/mL peaked at 10 minutes at a concentration of 5.3 ng/ml. This was equivalent to the Nicorette gum (5.9 ng/mL) which peaked at 45 minutes. The Tobacco Gold nicotine free base 3 mg/mL product peaked at 10 minutes with a plasma level of 1.9 ng/mL, less than the Nicorette gum. The plasma levels were proportional to the nicotine strength irrespective of the form (lactic acid salt or free-base) demonstrating that nicotine form (either salt or free-base) has no effect on nicotine absorption.
With this objective in mind, this poster aims at providing key learning from ISO 13485:2016 and QSR (21 CFR 820) that can be applied to device development intended for PMTA, MRTP, and NNHP submissions.
Ed Carmines, Karen Carmines, Lise Fraissinet, Naama Levy-Cooperman
Affiliations: Chemular, Inc, Hudson, MI, Altreos Research Partners Inc, Toronto, CN