Nicotine forms: why and how do they matter in nicotine delivery from electronic cigarettes?

ABSTRACT

Introduction

Unregulated e-cigarette devices and their nicotine content have amplified the potential of e-cigarettes as addictive agents. Several e-cigarette-related parameters have been identified altering nicotine’s absorption profile, so their potential effects on addiction should be considered. Of these factors, nicotine forms (protonated and free base) play a significant role in the addiction potential yet their impact on nicotine’s absorption has been studied with limited research.

Areas covered

Current review aims to emphasize on the possible mechanism behind different absorption profiles of nicotine forms considering their physical states (droplet and vapor phase) and the aerosol particle size, their analysis in e-cigarette research and the regulatory attention warranted by them to combat nicotine addiction in the population due to e-cigarettes.

Expert opinion

The protonated form of nicotine is being correlated with the smooth sensory effects and high nicotine absorption as compared to free base nicotine. With the introduction of nicotine salts, which yield mostly the protonated form, the youth popularity of e-cigarettes has spiked exponentially. While it is important to control nicotine levels in e-cigarette products, attention should also be given to the nicotine forms present in these products in order to address nicotine addiction in the population.

KEYWORDS:

• Electronic cigarettes
• nicotine delivery
• free base nicotine
• nicotine salt
• aerosol
• battery power
• addiction
• e-liquids

Article highlights

• Nicotine delivery by e-cigarettes has become a matter of concern due to increasing addiction of the youth to these products.

• Nicotine delivery by e-cigarettes is affected by several factors. Of these factors, nicotine form, i.e. free base or protonated, is one of the important factors which has shown to have different sensory and absorption effects.

• The research on nicotine forms is limited and studies have reported contradictory results about absorption profiles of nicotine forms.

• Various analytical approaches are being studied for the determination of free base or protonated fractions of total nicotine in these products.

• Regulatory attention to nicotine forms is warranted to address nicotine addiction caused by e-cigarettes.

This box summarizes key points contained in the article.

Abbreviations

NA - Not Applicable, Nic - Free base nicotine, NicH⁺ - Protonated nicotine, e-cig - electronic cigarette, PG - Propylene Glycol, VG - Vegetable Glycerin, MMAD- Mass Median Aerodynamic Diameter, VMAD- Volumetric Median Aerodynamic Diameter, MMD- Mass Median Diameter, CMD- Count Median Diameter

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

M Halquist is funded by NIDA (2P30DA033934-06) and received a small grant from the Virginia Youth Tobacco Projects Small Grants Program. L Golshahi received a pilot study grant from the Center for the Study of Tobacco Products under the main grant: U54DA036105. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by the Virginia Youth Tobacco Projects Small Grants Program for research funding and [2P30DA033934-06] (The Central Virginia Center on Drug Abuse Research, NIDA), and additional funding through the Virginia Foundation for Healthy Youth, Youth Tobacco Prevention grants program. The content is solely the responsibility of the authors and does not necessarily represent the views of the NIH or the FDA. Laleh Golshahi acknowledges the support of Center for the Study of Tobacco Products (CSTP) in the form of a pilot grant under