Transdermal Nicotine Delivery Systems: Multi-institutional Cooperative Bioequivalence Studies

Abstract

Nicotine transdermal delivery systems (nicotine-TDSs) have been evaluated clinically and found to provide effective assistance to smokers in smoking cessation with minimal occurrence of withdrawal symptoms. However, substantial skin reactions have been reported with the four nicotine-TDSs marketed recently. To reduce the skin reactions, a new type of nicotine-TDS has been recently developed. In vitro skin permeation studies demonstrated that this nicotine-TDS yields a constant skin permeation profile with a rate of permeation across the human cadaver skin comparable to the steady-state permeation rates attained by Habitrol™ and Nicoderm® systems. Clinical studies completed in two ethnic groups have demonstrated that this newly-developed nicotine-TDS is clinically effective and has yielded minimal skin irritation. As part of technical transfer program, a clinical study was initiated in 18 non-obese non-smoking Taiwanese, using Latin-square design, to compare the systemic bioavailability and pharmacokinetic profile of nicotine delivered transdermally from the nicotine-TDSs fabricated at technology licensee (Sintong nicotine-TDS) in comparison with that from the technology developer (TBS nicotine-TDS), using one marketed nicotine-TDS (Habitrol™ system) as the reference product. In vitro release and skin permeation studies of nicotine from the nicotine-TDSs manufactured at both licensor and licensee were found similar in kinetic profiles and comparable in rates. Since the patch size of these nicotine-TDSs studied was smaller than the marketed product used (10 cm² for both Sintong and TBS nicotine-TDSs, versus 20 cm² for Habitrol™ system), the daily doses of nicotine delivered to the volunteers are equivalent between Sintong and TBS nicotine-TDSs [9.58 (± 2.23) vs. 8.76 (± 1.88) mg/day/patch] but are lower than that from Habitrol™ system [15.13 (± 4.05) mg/day/patch]. Thus, for the statistical analysis of the pharmacokinetic parameters obtained need to be corrected for the difference in patch size and daily nicotine dose delivered. The results of statistical analysis suggested that Sintong and TBS nicotine-TDSs are bioequivalent to Habitrol™ system.