Low frequency sonophoresis mediated transdermal and intradermal delivery of ketoprofen

Abstract

The objective of this study was to test low frequency sonophoresis at 20kHz for delivery of ketoprofen into and across the skin. Permeation studies were carried out in vitro on excised hairless rat skin over a period of 24h using Franz diffusion cells after which, skin samples were subjected to skin extraction to quantify the amount of drug present in skin. Parameters like ultrasound application time, duty cycle coupling medium and distance of ultrasound horn from skin were optimized. Transepidermal water loss (TEWL) was measured to indicate the extent of barrier disruption following sonophoresis. Confocal microscopy was used to visualize dye penetration through sonophoresis treated skin. Application of ultrasound significantly enhanced permeation of ketoprofen from 74.87±5.27μg/cm2 for passive delivery to 491.37±48.78μg/cm2 for sonophoresis. Drug levels in skin layers increased from 34.69±7.25μg following passive permeation to 212.62±45.69μg following sonophoresis. TEWL increased from 31.6±0.02 (passive) to 69.5±12.60 (sonophoresis) indicating disruption of barrier properties. Confocal microscopy images depicted enhanced dye penetration through sonophoresis treated skin confirming barrier disruption. Low frequency sonophoresis with optimized ultrasound parameters can be effectively used to actively enhance transdermal and topical delivery of ketoprofen.