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.

Keywords

• oral tobacco derived nicotine (OTDN) pouches
• snus
• nicotine release
• nicotine dissolution
• nicotine extraction
• equivalence