In vitro phonophoresis: effect of ultrasound intensity and mode at high frequency on NSAIDs transport across cellulose and rabbit skin membranes.

The objective of this study was to evaluate the effect of intensity, mode, and duration of ultrasound application on the transport of three nonsteroidal anti-inflammatory drugs (NSAIDs) across cellulose membrane and rabbit-skin. Ibuprofen, piroxicam and diclofenac sodium were used as the model drugs. Studies were performed in vitro using a modified Franz diffusion assembly adapted to a therapeutic ultrasound transducer. Ultrasound had a significant and positive effect on the transport of the model NSAIDs across cellulose and rabbit skin membranes. Increasing ultrasound intensity from 0.5 to 3.0 W/cm2 led to a proportional increase in drug transport. Continuous ultrasound mode was more effective in enhancing drug transport than the pulsed mode. Diclofenac sodium had the least flux and permeability coefficient. This was attributed to its comparatively lower pKa value that renders the drug more ionizable in the buffer solution, consequently reducing its selective penetration through the membranes. This study demonstrated the therapeutic potential of ultrasound in transdermal delivery of NSAIDs and the synergistic effect of temperature and ultrasound operational parameters on drug transport.