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Purpose: The objective of this study was to test low frequency sonophoresis as an active enhancement technology for
transdermal and topical delivery of ketoprofen and to optimize ultrasound parameters for delivery.
Methods: Sonophoresis was carried out with a sonicator operating at 20 KHz frequency and intensity of 6.9 W/sq.cm (Sonics
VCX 500, Sonics and Materials, Newtown, CT). Donor formulation was saturated solution of ketoprofen in 50 percent
propylene glycol containing 3.5 mg/ml drug. Vertical Franz diffusion cells were used to study transdermal and topical delivery
of ketoprofen in vitro. Permeation studies were carried out on excised hairless rat skin over a period of 24 hours. Ultrasound
application time, duty cycle and coupling medium were optimized. Aluminum foil pitting was carried out to confirm acoustic
cavitation as the mechanism of enhanced sonophoretic delivery. Transepidermal water loss measurements (TEWL) were
performed to measure the extent of barrier disruption following sonophoresis. Confocal microscopy was used to visualize dye
penetration through sonophoresis treated skin.
Results: Application of ultrasound (2 minutes, 1% SLS coupling medium) significantly enhanced permeation of ketoprofen
from 74.87±5.27 μg/sq.cm for passive delivery to 491.37±48.78 μg/sq.cm for sonophoresis. The lag time for delivery reduced
from 6 hours for passive permeation to 2 hours for sonophoresis. Drug levels in underlying skin layers increased from
34.69±7.25 μg following passive permeation to 175.04±20.56 μg following sonophoresis. TEWL increased from 31.6±0.02
(passive) to 69.5±12.60 (optimized sonophoresis conditions) indicating disruption of barrier properties. Confocal microscopy
images depicted enhanced dye penetration through sonophoresis treated skin hence confirming barrier disruption.
Conclusions: Low frequency sonophoresis with optimized ultrasound parameters can be effectively used to actively enhance
transdermal and topical delivery of ketoprofen.