In vitro investigations of drug release and penetration--enhancing effect of ultrasound on transmembrane transport of flufenamic acid.

Although topical drugs are usually applied at a convenient site, the target for the drug interaction may be systemic. Phonophoresis is the use of ultrasound to enhance the delivery of topical applied drugs. The purposes of our study were to investigate the in vitro penetration and the in vivo transport of flufenamic acid in dependence of ultrasound. Percutaneous absorption studies are performed in various in vitro models to determine the rate of drug absorption via the skin. We designed a phonophoretic drug delivery system to investigate the influence of ultrasound on transmembrane transport of different drugs. We investigated the absorption of flufenamic acid in a buffer medium in dependence of ultrasound energy and application time. For evaluating membrane penetration of flufenamic acid, the concentration range of buffer solution was measured. Ultrasound energy was supplied for between 5 and 30 min at a range of intensities up to 1.5 W/cm2, energy levels commonly used for therapeutic purpose. The pronounced effect of ultrasound on the transmembrane absorption of the drug was observed at all ultrasound energy levels studied. The time of application was found to play an important role in delivery and transport of drug. Dependent on time, we observed a rise of temperature up to 4.5 degrees C. It appears that there was no difference between an intensity of 0.3 and 1.5 W/cm2 and the measured drug concentrations in solution. The highest penetration was observed at an intensity of 1.0 W/cm2 after 30 min. These results were not significantly different from concentration measurements after 30 min and 0.5 and 1.5 W/cm2. It seems that the arise of drug concentration is caused by effects of temperature and by variation of membrane delivery in dependence of temperature. Using this in vitro model we note it is possible to compare the transdermal penetration and absorption of commercial flufenamic ointment in volunteers.