Heat effects on drug delivery across human skin

Abstract

Introduction Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in vitro and in vivo methods to study them are of significant value to the development and evaluation of drug products dosed to the skin. Areas covered This review provides an overview of the underlying mechanisms and the observed effects of heat on the skin and on transdermal/topical drug delivery, thermoregulation and heat tolerability. The designs of several in vitro and in vivo heat effect studies and their results are reviewed. Expert opinion There is substantial evidence that elevated temperature can increase transdermal/topical drug delivery. However, in vitro and in vivo methods reported in the literature to study heat effects of transdermal/topical drug products have utilized inconsistent study conditions, and in vitro models require better characterization. Appropriate study designs and controls remain to be identified, and further research is warranted to evaluate in vitro-in vivo correlations and the ability of in vitro models to predict in vivo effects. The physicochemical and pharmacological properties of the drug(s) and the drug product, as well as dermal clearance and heat gradients may require careful consideration.

Cold atmospheric pressure plasmas in dermatology: Sources, reactive agents, and therapeutic effects

“…[ 113 ] Longer exposure of skin to a temperature higher than 43°C can lead to the formation of blisters. [ 116 ] Therefore, fast and gentle heating by the plasma can increase skin permeability without damaging deeper tissues. Importantly, the effects of plasmaporation on the skin barrier properties are largely or completely reversible.…”

Characterization of Temperature Profiles in Skin and Transdermal Delivery System When Exposed to Temperature Gradients In Vivo and In Vitro

“…in vivo studies exploring heat effects on TDS have utilized differing conditions where durations of elevated temperature exposure have ranged from 5 min to 10 h, test temperatures have ranged from 39°C in a hot tub to air temperature of 90°C in a sauna. The heat sources themselves have also represented fundamentally different scenarios ranging from an internal heat source induced by strenuous exercise to various external sources of heat (e.g., heating lamps, electric heating pads or blankets, heated water baths, saunas) (12). A variety of different protocol parameters have also been utilized for in vitro studies with different durations and frequencies of elevated temperature exposure, elevated temperature ranges, and methods of exposure.…”

Enhancement of Percutaneous Absorption on Skin by Plasma Drug Delivery Method

“…It was found out that fast heating of skin can increase skin permeability without damaging deeper tissues. Investigation of high temperatures of up to 315°C applied to skin for 100 ms, 1 s and 5 s showed small variations between drug deliveries of calcein [82]. Exposure for 1 s or 5 s should be sufficient to equalize temperature in the full thickness of skin, but the 100 ms exposure should have influence only on stratum corneum.…”

“…Thermal conditions that cause burns of the skin are functions of the time and method of how the skin is exposed to the heat. Longer exposure of skin to a temperature higher than 43°C can lead to the formation of blisters [82]. It was found out that fast heating of skin can increase skin permeability without damaging deeper tissues.…”