Development of a model to predict nicotine pharmacokinetics from oral nicotine pouches

Oral Nicotine Pouches (ONPs) have emerged as a promising non-combustible nicotine alternative to traditional tobacco products. Regulatory approval of ONPs in the United States requires comprehensive studies to demonstrate that new tobacco products are appropriate for the protection of public health. Conventional nicotine pharmacokinetic (PK) studies typically depend on expensive and time-intensive human trials. To address this challenge, a predictive PK model to forecast buccal absorption of nicotine from ONPs was developed using in vitro data. A novel dissolution method employing a µDISS Profiler was used to generate nicotine dissolution and dynamic pH profiles for three commercially available ONPs: ZYN Cool Mint 6 mg, DRYFT Spearmint 7 mg, and VELO Mint 4 mg. The model integrates experimental in vitro data with established nicotine PK parameters to predict clinical PK profiles. It effectively forecasted key PK metrics, including AUC, C max , and T max , while emphasizing the pivotal role of buccal/saliva pH in nicotine permeability and absorption. This methodology shows promise as a reliable, cost-efficient, and time-saving potential alternative to traditional clinical studies, offering potential data and insights for regulatory applications and product development.