The Effect of Heating and the Combination of Heating and d-Limonene on the Percutaneous Permeation of Some Drugs

As an innocuous strategy of accelerating the skin penetration of drugs, heating the skin surface at 41°C was adopted. The effect of heating on the drug penetration was examined by using Wistar rat skin in vitro. The enhancing effect of combining heating and d-limonene was also investigated. The electric heating of the skin surface at 41°C enhanced the flux of bupranolol (BP), indomethacin (IM), and ketoprofen (KP) by 1.8- to 2.4-fold, but the heating only slightly increased the flux of terbutaline (TB) sulfate, a water-soluble drug. The combination of heating and d-limonene enhanced the penetration of all drugs tested through the skin by 2- to 3-fold compared with that in the presence of the enhancer alone. The synergic effect of heating and d-limonene was little observed except for TB sulfate. As a result, heating at 41-42°C is useful as a nontoxic enhancing method for the percutaneous permeation of drugs.