Pharmacokinetic characterization of three novel 4-mg nicotine lozenges

Objective: Nicotine replacement therapy (NRT) increases the probability of smoking cessation. This study was conducted to determine if three prototype 4-mg nicotine lozenges produced locally in India were bioequivalent to a globally marketed reference product, Nicorette(®) 4-mg nicotine lozenge. Materials and methods: Healthy adult smokers (N = 39) were treated with three prototype 4-mg nicotine lozenges in comparison with a reference 4-mg lozenge in this single-center, randomized, open-label, single-dose, 4-way crossover study. Pharmacokinetic sampling was obtained to test for bioequivalence using maximal plasma concentration (C(max)) and extent of absorption (AUC(0–t)). Secondarily, AUC(0–∞), time to maximal plasma concentration (t(max)), half-life (T(1/2)), elimination rate constant (K(el)), and safety of the prototype lozenges versus the reference lozenge were compared. Results: Each prototype 4-mg nicotine lozenge was found to be bioequivalent to the reference 4-mg nicotine lozenge based on the ratio of geometric means and 90% confidence intervals for C(max), AUC(0–t), and AUC(0–∞). Although t(max) was significantly longer for prototype III, all four lozenges achieved maximum plasma nicotine concentrations at a median of 1.5 hours. The safety profiles of the three prototype 4-mg lozenges did not differ from that of the 4-mg reference product. Conclusion: Each prototype 4-mg nicotine lozenge was bioequivalent to the reference 4-mg nicotine lozenge and was well tolerated. Furthermore, as these bioequivalent prototypes differed in in-vitro dissolution profiles, these data suggest that performance from the in vitro method deployed is not a firm predictor of pharmacokinetic behavior.