Formulation of smokeless tobacco products with a wide range of pH to study nicotine pharmacokinetics and pharmacodynamics.
Level 5 - mechanism / opinion, no new human data
Laboratory formulation and stability study without human subjects.
PubMed 35850567 · doi:10.1080/10837450.2022.2102650
What was done
Researchers developed four investigational moist snuff smokeless tobacco products that varied solely by pH for future use in clinical pharmacokinetic trials. A commercial product (Copenhagen Long Cut Original, baseline pH 7.7) was modified using citric acid monohydrate (23 mg/g tobacco) or sodium carbonate (4.6 and 11 mg/g) to create test products with target pH values of 5.0, 8.2, and 8.6 alongside the unmodified pH 7.7 product. Samples were packaged in individual ~2 g aluminum foil pouches and stored frozen at -20 °C. Stability of pH, nicotine concentration, tobacco-specific nitrosamines, moisture content, and mold and yeast counts was measured for up to 19 months.
What was found
The formulations remained stable during the 19-month storage period at -20 °C. Product pH values remained within 0.1 pH units of baseline and never deviated by more than 0.2 units. Baseline nicotine concentration averaged 9.07 mg/g, and maximal deviations from baseline across the four products averaged 0.30 mg/g. Tobacco-specific nitrosamines, moisture content, and yeast and mold counts did not materially change throughout testing.
Why it matters
This method establishes a reliable protocol to isolate product pH as an independent variable in smokeless tobacco without altering other matrix components. It enables the preparation of stable, standardized investigational products needed to systematically evaluate the impact of pH on oral nicotine absorption kinetics in humans.
Limits
This is strictly an in vitro formulation and stability study; no clinical, pharmacokinetic, or pharmacodynamic testing in humans was conducted in this report. The abstract lacks explicit quantitative values for baseline and endpoint measurements of tobacco-specific nitrosamines, moisture content, and microbial counts, and the number of sample replicates tested is not stated. Stability findings are specific to the tested matrix and frozen storage conditions (-20 °C).
Cited by
- supports Zyn nicotine pouches contain sodium carbonate to raise pH and convert nicotine into its freebase form for enhanced gum absorption.