Effect of Ultrasound Intensity and Mode on Piroxicam Transport Across Three-Dimensional Skin Equivalent Epiderm™

Background: Transdermal drug delivery has many advantages compared to other routes. However, the barrier function of the stratum corneum limits the use of the skin as an administrative route for medications. Different methods were investigated to alter the barrier function of the stratum corneum and it was found that applying different ultrasound waves could enhance the skin's permeability. Objective: The aim of this work is to study the effect of ultrasonic waves on the alteration of skin natural barrier function, to improve the permeability of the skin to Piroxicam using three-dimension skin (EpiDermTM) as a skin model for the investigation. Method: The effect of ultrasound at 1 MHz and 20 kHz on the permeation of Piroxicam across the three-dimensional skin equivalent using a Franz diffusion cell, was evaluated and the concentration of Piroxicam in the receiving compartment was determined using liquid chromatography method. Results: The permeation of Piroxicam enhanced by 199% when therapeutic ultrasound at 1 MHz frequency was used. Significant permeation enhancement was also found upon utilizing low frequency sonophoresis at 20 kHz (427%) with no apparent damage to the membrane. Conclusion: Sonophoresis has a positive effect on enhancing skin permeability. The enhancement level was largely dependent on the sonication factors; frequency, intensity and length of treatment. Multiple mechanisms of action might be involved in permeation improvement of the piroxicam molecule. Those mechanisms are largely dependent on the ultrasonic conditions.