In vitro investigations of drug release and penetration--enhancing effect of ultrasound on transmembrane transport of flufenamic acid.
Percutaneous absorption studies are performed in various in vitro models to determine the rate of drug absorption via the skin. We designed an phonophoretic drug delivery system to investigate the influence of ultrasound on transmembrane transport of different drugs. Phonophoresis is defined as the migration of drug molecules, contained in a contact agent, through the skin under the influence of ultrasound. 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. Flufenamic acid was determined by using a fluorimetric method. Ultrasound energy was supplied for between 5 and 30 min at a range of intensities (0; 0.3; 0.6; 0.9; 1.2; 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 level studied. The time of application was found to play an important role in delivery and transport of drug. Dependent on time, we observed an arise of temperature up to 4.5 degrees. 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 in 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.
Department of Clinical Pharmacology, Friedrich Schiller University Jena, Germany.
M
M
Hippius
U
U
Smolenski
C
C
Uhlemann
U
U
Schreiber
A
A
Hoffmann
D001692:Biological Transport; D005439:Flufenamic Acid / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D015612:Phonophoresis / Q000379:methods*; D013696:Temperature; D013997:Time Factors
D008567:Membranes, Artificial; D005439:Flufenamic Acid