The Effects of Iontophoresis and Electroporation on Transdermal Delivery of Indomethacin Evaluated In Vitro and In Vivo
Ren-Jiunn Wang1, Yaw-Bin Hung1, Pao-Chu Wu1, Jia-You Fang2 AND Yi-Hung Tsai1*
1. Graduate Institute of Pharmaceutical Sciences, College of Pharmacy, Kaohsiung Medical University,
100 Shih-Chuan 1st Rd., Kaohsiung 807, Taiwan, R.O.C.
2. Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.
(Received: July 10, 2006; Accepted: December 6, 2006)
Abstract
The objective of this study was to evaluate the transdermal delivery of indomethacin in vitro and in vivo enhanced by iontophoresis and/or electroporation through several barriers. Excised Wistar rat skin, pig skin, human epidermal membrane and cellulose membrane were tested for the in vitro indomethacin permeation, whereas drug concentration of in the plasma was analyzed to monitor the percutaneous absorption in Wistar rat in vivo. Iontophoresis enhanced the in vitro transdermal delivery of indomethacin as compared to the passive diffusion. Pulsing of high voltages, as known as electroporation, followed by iontophoresis did result in a synergistic effect in contrast to iontophoresis or electroporation alone. The in vitro result indicated that higher drug permeation could be induced during and after the application of iontophoresis. In some case, the permeation could benefit from the electroporation in term of cumulative amount within 12 hr. Furthermore, the combination of electroporation and iontophoresis resulted in a higher permeation amount than iontophoresis or electroporation alone did. Both iontophoresis and the combination protocol could reduce interspecies difference in vitro. The in vivo results were similar to that of in vitro ones. Iontophoresis and electroporation/iontophoresis resulted in higher AUC (area under curve) of blood concentration profiles of indomethacin. In addition, the combination protocol significantly induced higher transepidermal water loss (TEWL). It is concluded that the in vivo permeation results did correspond to the enhancement efficiency of the in vitro experiments.
Key words: transdermal delivery, indomethacin, iontophoresis, electroporation, TEWL