Effect of local controlled heat on transdermal delivery of nicotine.

Skin permeability and local blood perfusion are important factors for transdermal drug delivery. Application of heat is expected to enhance microcirculation and local perfusion and/or blood vessel permeability, thus facilitating drug transfer to the systemic circulation. In addition, heating prior to or during topical application of a drug may facilitate skin penetration, increase kinetic energy, and facilitate drug absorption. The aim of the present study was to investigate whether application of controlled local heat would enhance transdermal delivery from the nicotine patch mounted on the upper arm of ten healthy non-smoking male Caucasian subjects. Local skin perfusion was monitored using Laser Doppler Imaging (LDI) at baseline (32 °C) and following application of local controlled heat (43 °C) on the upper arm, where the patch was placed. The residue of the nicotine patches was then examined by High-Performance Liquid Chromatography (HPLC) to indicate the uptake of nicotine from the patch due to the local controlled heat. Controlled heat application (43°C) caused significant cutaneous hyperaemia (up to 9 folds increase in skin perfusion) with an increase in nicotine uptake (up to 13 folds). The method was well tolerated without causing any pain or discomfort. These data suggest that controlled heat application, which is a simple, non-invasive method, can significantly enhance local skin perfusion and drug uptake from patches.