title: Low frequency sonophoresis mediated transdermal and intradermal delivery of ketoprofen.
abstract: The objective of this study was to test low frequency sonophoresis at 20 kHz 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 ± 5.27 μg/cm(2) for passive delivery to 491.37 ± 48.78 μg/cm(2) for sonophoresis. Drug levels in skin layers increased from 34.69 ± 7.25 μg following passive permeation to 212.62 ± 45.69 μg 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.
authors.affiliation: Department of Pharmaceutical Sciences, Mercer University, Atlanta, GA, United States.
authors.forename: Anushree
authors.initials: A
authors.lastname: Herwadkar
authors.forename: Vishal
authors.initials: V
authors.lastname: Sachdeva
authors.forename: Leslie F
authors.initials: LF
authors.lastname: Taylor
authors.forename: Herb
authors.initials: H
authors.lastname: Silver
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Banga
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D007660:Ketoprofen / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D010539:Permeability; D015612:Phonophoresis; D051381:Rats; D054772:Rats, Hairless; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D013997:Time Factors; D014870:Water Loss, Insensible
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D007660:Ketoprofen; C028913:dodecyl sulfate; C007740:fluorexon