A novel thermo-mechanical system enhanced transdermal delivery of hydrophilic active agents by fractional ablation

Int J Pharm. 2016 Sep 25;511(2):821-30. doi: 10.1016/j.ijpharm.2016.07.070. Epub 2016 Jul 29.


The Tixel is a novel device based on a thermo-mechanical ablation technology that combines a sophisticated motion and a temperature control. The fractional technology is used to transfer a very precise thermal energy to the skin thereby creating an array of microchannels, accompanying by no signs of pain or inconvenience. This study aimed to evaluate the effect of the Tixel on the skin permeability of three hydrophilic molecular models: verapamil hydrochloride, diclofenac sodium, and magnesium ascorbyl phosphate. Tixel's gold-platted stainless steel tip heated to a temperature of 400°C was applied on skin for 8ms or 9ms at a protrusion of 400μm (the distance in which the tip protrudes beyond the distance gauge). The experiments were carried out partly in vivo in humans using a fluorescent dye and a confocal microscopy and partly in vitro using porcine skin and a Franz diffusion cell system. The results obtained in this study have shown that (a) no significant collateral damage to the skin tissue and no necrosis or dermal coagulation have been noted, (b) the microchannels remained open and endured for at least 6h, and (c) the skin permeability of hydrophilic molecules, which poorly penetrate the lipophilic stratum corneum barrier, was significantly enhanced by using Tixel's pretreatment.

Keywords: Diclofenac; Fractional skin ablation; Magnesium ascorbyl phosphate; Percutaneous permeation; Transdermal drug delivery; Verapamil.

MeSH terms

  • Animals
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / analogs & derivatives
  • Ascorbic Acid / pharmacokinetics
  • Diclofenac / administration & dosage
  • Diclofenac / pharmacokinetics
  • Drug Delivery Systems / instrumentation*
  • Hot Temperature
  • Humans
  • Injections, Intradermal / instrumentation*
  • Phenolsulfonphthalein / pharmacology
  • Skin / anatomy & histology
  • Skin / drug effects
  • Skin Absorption*
  • Swine
  • Verapamil / administration & dosage
  • Verapamil / pharmacokinetics


  • Diclofenac
  • ascorbate-2-phosphate
  • Verapamil
  • Phenolsulfonphthalein
  • Ascorbic Acid