The In Vitro and In Vivo Transdermal Delivery of NSAIDs Enhanced by Iontophoresis and Electroporation

• Main Authors: Ren-Jiunn Wang, 王仁俊
• Other Authors: Yi-Hung Tsai
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/06842237027503268834

博士 === 高雄醫學大學 === 藥學研究所博士班 === 95 === The aim of this present study was to investigate the influence of iontophoresis, electroporation and their combination on the transdermal permeation. Several NSAIDs including diclofenac, indomethacin, ketoprofen, ketorolac, piroxicam and two meloxicam salts were chosen as model drugs. Indomethacin and meloxicam were both chosen to carry out the in vitro and in vivo study. Cellulose membrane, Wistar rat skin, pig skin, and HEM (human epidermal membrane) were chosen as the barrier of in vitro study. Wistar rat was chosen as the animal model of in vivo study. In comparison of chemical enhancers and physical enhancers on the release of ketoprofen, the enhancement effect depended on the condition. However, the physical enhancers could reduce the lag time of the release of ketoprofen. The flux resulted from iontophoresis, electroporation and combination protocol was reversely dependent on the M.W. of model drug. It was also found that the synergistic effect of combination protocol presented in the condition of enough voltage of electroporation with maximally acceptable value of current density of iontophoresis in the preliminary study. Iontophoresis and combination protocol could enhance the in vitro and in vivo transdermal permeation of indomethacin, but the enhancement of electroporation was limited. The combination protocol produced synergistic effect. Iontophoresis and combination protocol could also enhance the in vitro and in vivo transdermal permeation of meloxicam salts. However, electroporation could also enhance the permeation in the in vivo study. Meloxicam potassium might benefit more from the electrical protocols than meloxicam sodium. Rather than the individual protocols, the combination of electroporation/iontophoresis induced more TEWL (transepidermal water loss), and the phenomenon could return to normal. It was concluded that iontophoresis and combination protocol could enhance the transdermal permeation of model drugs. The enhancement of electroporation and the synergistic effect of combination protocol depended on the drug.