Journal of Bioequivalence & Bioavailability

Abstract

Bioequivalence of Two Different Nicotine Chewing Gum Formulations of Two Different Strengths (2 mg and 4 mg) in Indian Healthy Adult Human Male Smoker Subjects

Muneesh Garg, Raghu Naidu, Krishnan Iyer and Ratnakar Jadhav

Nicotine Mint Flavored Chewing Gums are used to aid smokers wishing to quit or reduce prior to quitting. The aim of these two studies was to determine the bioequivalence of two test and two reference formulations of Nicotine 2 mg and 4 mg Mint Flavored Chewing Gum. Both of these two studies were single dose, randomized, 2-period, 2‑sequence, laboratory-blinded, crossover design conducted in two different set of 54 healthy adult Indian male subjects each under fasting conditions with a washout period of 8 days (for 2 mg study) and 9 days (for 4 mg study). Study formulations were administered after a 10-hour overnight fast. Blood samples for pharmacokinetic profiling were taken post-dose up to 24 hours. Safety was evaluated through the assessment of adverse events, and laboratory tests. Plasma concentrations of Nicotine were determined with a validated LC-MS/MS method. Bioequivalence between the products was determined by calculating 90% confidence intervals (90% CI) for the ratio of Cmax and AUC0-t values for the test and reference products, using logarithmic transformed data. The 90% CI of Nicotine were 93.71-113.45, 89.95-112.68 and 92.90-115.98 for Cmax, AUC0-t and AUC0-∞ respectively for Nicotine 2 mg Mint Flavored Chewing Gum study. The 90% CI of Nicotine were 88.68-102.76, 91.48-109.00 and 91.14-111.66 for Cmax, AUC0-t and AUC0-∞ respectively for Nicotine 4 mg Mint Flavored Chewing Gum study. Since the 90% CI for Cmax and AUC0-t were within the 80-125% interval, it was concluded that the two test and two reference formulations of Nicotine 2 mg and 4 mg Mint Flavored Chewing Gum are bioequivalent in their rate and extent of absorption.