title: Response surface method: a novel strategy to optimize iontophoretic transdermal delivery of thyrotropin-releasing hormone.
abstract: OBJECTIVE
  To maximize the iontophoretic transdermal delivery rate of thyrotropin-releasing hormone (TRH) facilitated by periodically monophase-pulsed current across excised skin.
  
  
  METHODS
  The pH of the buffer, the ionic strength in the solution, the frequency of the periodically monophase-pulsed current and the current on/off ratio were chosen as the key variables. A response surface method was applied to optimize the transdermal delivery rate of TRH under different operational conditions.
  
  
  RESULTS
  The optimum operating conditions were achieved via experimentation based on the response surface method by systematically adjusting the pH of the buffer, the ionic strength in the solution, the current amplitude, frequency and the active temporal ratio of the pulsed current. The rate of permeation of TRH crossing the skin during iontophoresis varied from two to ten-fold, depending on operating conditions.
  
  
  CONCLUSIONS
  Only a few steps, two in this work, were needed to reach the optimal. The response surface near the region of the maximal point was thoroughly described with a quadratic function. A maximal transdermal rate of permeation of TRH, 103.2 micrograms h-1 cm-2, was obtained when the donor solution was at pH = 7.0, ionic strength = 0.037, and with a periodically monophase-pulsed current iontophoresis with duty cycle = 75%. The effect of pulse frequency was not statistically significant.
authors.affiliation: Center for Biomedical Engineering, College of Medicine, National Taiwan University, Taipei, Republic of China.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Huang
authors.forename: S M
authors.initials: SM
authors.lastname: Wu
authors.forename: C Y
authors.initials: CY
authors.lastname: Wang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004586:Electrophoresis; D004817:Epidermis / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007478:Iontophoresis; D016014:Linear Models; D009994:Osmolar Concentration; D011817:Rabbits; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D013499:Surface Properties; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D013973:Thyrotropin-Releasing Hormone