Use of sorption promoters to increase systemic absorption of coumarin from transdermal drug delivery systems.
In previous communications it was shown that coumarin is transdermally well absorbed. Increasing the application area for a coumarin ointment from 5 cm2 to 30 cm2, the absolute bioavailability increases from 8.6% to 66%. Using a transdermal drug delivery system (TDDS) based on an elastomer matrix, the absolute bioavailability was 21.9%. By selecting a proper sorption promoter (Labrafil), the absolute bioavailability increased to 71%. No correlation was found between tlag, flux or amount permeated obtained from ex vivo flux measurements, and the in vivo parameters Cmax and AUC. Whereas the bioavailability of a large area application of coumarin ointment is practically the same as with a small TDDS, the latter one is preferred to maintain a therapeutic concentration over a 24 h or 48 h period.
Ritschel
W A
WA
Division of Pharmaceutics and Drug Delivery Systems, University of Cincinnati Medical Center, OH.
Barkhaus
J K
JK
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D003374:Coumarins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004058:Diffusion; D004339:Drug Compounding; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D012995:Solubility
D003374:Coumarins