Development of an optimised application protocol for sonophoretic transdermal delivery of a model hydrophilic drug.

It has now been known for over a decade that low frequency ultrasound can be used to effectively enhance transdermal drug penetration - an approach termed sonophoresis. Mechanistically, acoustic cavitation results in the creation of defects in the stratum corneum that allow accelerated absorption of topically applied molecules. The aim of this study was to develop an optimised sonophoresis protocol for studying transdermal drug delivery in vitro. To this end, caffeine was selected as a model hydrophilic drug while porcine skin was used as a model barrier. Following acoustic validation, 20kHz ultrasound was applied for different durations (range: 5 s to 10 min) using three different modes (10%, 33% or 100% duty cycles) and two distinct sonication procedures (either before or concurrent with drug deposition). Each ultrasonic protocol was assessed in terms of its heating and caffeine flux-enhancing effects. It was found that the best regimen was a concurrent 5 min, pulsed (10% duty cycle) beam of SATA intensity 0.37 W/cm(2). A key insight was that in the case of pulsed beams of 10% duty cycle, sonication concurrent with drug deposition was superior to sonication prior to drug deposition and potential mechanisms for this are discussed.