Introducing a Novel Biorelevant In Vitro Dissolution Method for the Assessment of Nicotine Release from Oral Tobacco-Derived Nicotine (OTDN) and Snus Products

Abstract

The rate at which oral tobacco-derived nicotine (OTDN) and snus pouches release nicotine into saliva is crucial to determine product performance. As no standardized method is available for this purpose, this study sought to develop a biorelevant dissolution method that could both discriminate between different products and predict in vivo behavior. Using a μDISS Profiler™ as a surrogate for the US Pharmacopoeia standard apparatuses and a custom-made sinker, nicotine release from an OTDN pouch product (ZYN® Dry Smooth) and a snus product (General® Pouched Snus White Portion Large) was determined in biorelevant volumes (10 mL) of artificial saliva. In addition, nicotine extraction in vivo was measured for both products. Strikingly, the method showed distinct dissolution curves for OTDN and snus pouches, and the nicotine release observed in vitro did not significantly differ from the nicotine extracted in vivo. The custom-made sinker was designed to accommodate both loose and pouched oral tobacco/nicotine products, and thus the proposed in vitro dissolution method is suitable to assess nicotine release from OTDN and snus pouches. Apart from providing individual dissolution curves, the method was also able to predict in vivo nicotine extraction. Thus, this method could serve as a (biorelevant) monograph for product equivalence studies.

Oral nicotine pouches with an aftertaste? Part 2: in vitro toxicity in human gingival fibroblasts

“…Further, the novel products may exert local cytotoxic effects especially in the oral mucosa. Few studies addressed these issues in the past, most of them published by manufacturers on their proprietary products (Aldeek et al 2021 ; Bishop et al 2020 ; East et al 2021 ; Knopp et al 2022 ). Only one study was without industry involvement (Shaikh et al 2022 ).…”

Method Development and Applications for Reduced-Risk Products

“…In the second manuscript, Knopp et al developed a biorelevant dissolution method to study the nicotine release from OTDN nicotine pouches and portioned smokeless tobacco products (e.g., pouched snus) [23]. The in vitro release of nicotine was investigated in biorelevant volumes of artificial saliva using a custom-made dissolution apparatus.…”