Pharmaceutical Research

, Volume 13, Issue 4, pp 547–552 | Cite as

Response Surface Method: A Novel Strategy to Optimize lontophoretic Transdermal Delivery of Thyrotropin-releasing Hormone

  • Yi-You Huang
  • Shian-Min Wu
  • Cheng-Yi Wang


Purpose. 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 µg 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.

optimization iontophoretic transdermal delivery thyrotropin releasing hormone (TRH) response surface method 


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  1. 1.
    P. Wehrle, P. Nobelis, A. Cuine, and A. Stamm. Response Surface Methodology: An Interesting Statistical Tool for process Optimization and Validation: Example of Wet Granulation in a High-Shear Mixer. Drug Dev. Ind. Pharm., 19:1637–1653 (1993).Google Scholar
  2. 2.
    D. Vojnovic, M. Moneghini, and F. Rubessa. Optimization of Granulation in a High Shear Mixer by Mixture Design. Drug Dev. Ind. Pharm., 20:1035–1047 (1994).Google Scholar
  3. 3.
    B. Iskandarani, J. H. Clair, P. Patel, P. K. Shiromani, and R. E. Dempski, R.E., Simultaneous Optimization of Capsule and Tablet Formation Using Response Surface methodology. Drug Dev. Ind. Pharm., 19:2089–2101 (1993).Google Scholar
  4. 4.
    E. Senderak, H. Bonsignore, and D. Mungan. Response Surface methodology as an Approach to Optimization of an Oral Solution. Drug Dev. Ind. Pharm., 19:405–424 (1993).Google Scholar
  5. 5.
    Y. Y. Huang, S. M. Wu, C. Y. Wang, and T. S. Jiang. A strategy to optimize the operation conditions in iontophoretic transdermal delivery of pilocarpine, Drug Dev. Ind. Pharm., 21:1631–1648 (1995).Google Scholar
  6. 6.
    P. Wehrle and A. Stamm. Statistcal tools for process control and quality improvement in the pharmaceutical industry, Drug Dev. Ind. Pharm., 20:141–164 (1994).Google Scholar
  7. 7.
    Y. Y. Huang and S. M. Wu. Transdermal iontophoretic delivery of thyrotropin releasing hormone across excised rabbit pinna skin, Drug Dev. Ind. Pharm., 21: in press (1996).Google Scholar
  8. 8.
    M. Corbo, P. R. Wang, J. K. Li, and Y. W. Chien. Effect of propranolol on the myocardial contractility of normotensive and spontaneously hypertensive rabbits: relationship of pharmacokinetics and pharmacodynamics. J. Pharmacokinetics and Biopharmaceutics, 17:551–570 (1989).Google Scholar
  9. 9.
    R. R. Burnette and D. Marrero. Comparison between the iontophoretic and passive transport of thyrotropin releasing hormone across excised nude mouse skin. J. Pharm. Sci., 75:738–743 (1986).Google Scholar
  10. 10.
    J. B. Jaspan, E. Lever, K. S. Polonsky, and E. V. Cauter. In Vivo Pulsatility of Pancreatic Islet Peptides, Am. J. Physiol. 251:E215–E226 (1986).Google Scholar
  11. 11.
    D. S. Weigle. Pulsatile Secretion of Fuel-Regulatory Hormones. Diabetes. 36:764–775 (1987).Google Scholar
  12. 12.
    G. E. Box and N. R. Draper. Emperical model building and response surfaces. Wiley, New York, (1987).Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Yi-You Huang
    • 1
  • Shian-Min Wu
    • 2
  • Cheng-Yi Wang
    • 3
  1. 1.Center for Biomedical Engineering, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  2. 2.Department of Chemical EngineeingTunghai UniversityTai-chungTaiwan
  3. 3.Department of Internal Medicine, College of MedicineNational Taiwan UniversityTaipeiTaiwan, Republic of China

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