Ultrasound-enhanced diffusion into coupling gel during phonophoresis of 5-fluorouracil

Purpose: To investigate the competitive transport across skin and back-diff usion of 5-fluorouracil into coupling gel under the influence of ultrasound , heat-alone and Azone enhancement. Methods: The ultrasound effect on 5-flu orouracil penetration through whole rat skin was investigated in modified d iffusion cells using a commercial ultrasound generator which was calibrated with a bilaminar membrane hydrophone. Results: Ultrasonic dosimetry measur ements demonstrated that the skin membrane was subjected to a complex and u npredictable standing wave field which induced physiologically acceptable h eating of the tissue. Surprisingly, ultrasonication produced a decrease in percutaneous drug penetration. Quantification studies indicated that this e ffect was due to the diffusive loss of the hydrophilic substance 5-fluorour acil from the skin surface into the overlying volume of coupling gel. This phenomenon could be duplicated by the application of conductive heating, in dicating that the thermal effects of ultrasound were probably responsible f or accelerated 5-fluorouracil diffusion through the gel. Conclusion: This s tudy acutely demonstrates how formulation design of the donor vehicle/coupl ing gel may radically affect therapeutic efficacy in phonophoretic systems. Published by Elsevier Science B.V.