title: Heat effects on drug delivery across human skin.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Pharmaceutical Science and Research , School of Pharmacy, Marshall University , Huntington , WV , USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Hao
authors.affiliation: b Office of Research and Standards, Office of Generic Drugs , Center for Drug Evaluation and Research, United States Food and Drug Administration , Silver Spring , MD , USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: c Division of Pharmaceutical Sciences , James L Winkle College of Pharmacy, University of Cincinnati , Cincinnati , OH , USA.
authors.forename: S Kevin
authors.initials: SK
authors.lastname: Li
authors.affiliation: b Office of Research and Standards, Office of Generic Drugs , Center for Drug Evaluation and Research, United States Food and Drug Administration , Silver Spring , MD , USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Newman
authors.affiliation: c Division of Pharmaceutical Sciences , James L Winkle College of Pharmacy, University of Cincinnati , Cincinnati , OH , USA.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Kasting
authors.affiliation: b Office of Research and Standards, Office of Generic Drugs , Center for Drug Evaluation and Research, United States Food and Drug Administration , Silver Spring , MD , USA.
authors.forename: Sam G
authors.initials: SG
authors.lastname: Raney
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006358:Hot Temperature; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*
chemical_list: D004364:Pharmaceutical Preparations
keywords: dermal clearance; heat effect; heat exposure; patch; skin blood flow; topical drug products; transdermal delivery systems (TDS)