Ultrasound-enhanced diffusion into coupling gel during phonophoresis of 5-fluorouracil.
OBJECTIVE
To investigate the competitive transport across skin and back-diffusion of 5-fluorouracil into coupling gel under the influence of ultrasound, heat-alone and Azone enhancement.


METHODS
The ultrasound effect on 5-fluorouracil penetration through whole rat skin was investigated in modified diffusion cells using a commercial ultrasound generator which was calibrated with a bilaminar membrane hydrophone.


RESULTS
Ultrasonic dosimetry measurements demonstrated that the skin membrane was subjected to a complex and unpredictable standing wave field which induced physiologically acceptable heating of the tissue. Surprisingly, ultrasonication produced a decrease in percutaneous drug penetration. Quantification studies indicated that this effect was due to the diffusive loss of the hydrophilic substance 5-fluorouracil from the skin surface into the overlying volume of coupling gel. This phenomenon could be duplicated by the application of conductive heating, indicating that the thermal effects of ultrasound were probably responsible for accelerated 5-fluorouracil diffusion through the gel.


CONCLUSIONS
This study acutely demonstrates how formulation design of the donor vehicle/coupling gel may radically affect therapeutic efficacy in phonophoretic systems.
Meidan
V M
VM
Pharmaceutical Sciences Research Institute, Aston Pharmacy School, Aston University, Aston Triangle, Birmingham, UK.
Walmsley
A D
AD
Docker
M F
MF
Irwin
W J
WJ
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001381:Azepines / Q000494:pharmacology; D001692:Biological Transport; D002463:Cell Membrane Permeability; D002626:Chemistry, Pharmaceutical; D002855:Chromatography, Thin Layer; D004058:Diffusion; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D005782:Gels; D008297:Male; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D015612:Phonophoresis / Q000379:methods*; D011874:Radiometry; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012869:Skin Absorption; D012881:Skin Temperature; D014465:Ultrasonics
D000964:Antimetabolites, Antineoplastic; D001381:Azepines; D005782:Gels; D014677:Pharmaceutical Vehicles; C035229:laurocapram; D005472:Fluorouracil