Preclinical testing of flavors in e-vapor products - Part 2: Preparation and stability characterization of representative flavor mixtures
GLP guidelines require the characterization of test articles for preclinical biological studies to ensure the identity and composition are consistent from batch to batch and throughout the testing period. For e-vapor products, this would suggest that the analysis of individual ingredients, including various flavors and carriers, be conducted each time a formulation is made. In this study, we explored a unique approach to create concentrated mixtures (“pre-blends”) prior to making a final formulation (containing 38 flavors) to maximize stability and simplify the preparation procedure. The 38 flavor compounds were sub-divided into five (5) groups based on structural moiety, solubility and chemical reactivity (i.e., unreactive, electrophilic, nucleophilic, basic, acidic). These groups were used to make a total of 6 pre-blends with their long-term stability confirmed up to 4 weeks. At the same time, the pre-blends were mixed to make two types of final formulations containing all 38 flavor compounds, with and without nicotine. The final formulation was stable up to 3 days in the presence of nicotine and 10 days without nicotine. Our work demonstrates the benefit of creating stable and concentrated pre-blends to avoid daily formulation making thus reducing the frequency of batch characterization especially for repeated long-term dosing studies.