Release of chemical permeation enhancers from drug-in-adhesive transdermal patches.
There is only limited knowledge of how chemical permeation enhancers release from transdermal drug delivery systems of the drug-in-adhesive type. In this study, the release of eight commonly known enhancers from eight types of polymer adhesives was evaluated using Franz diffusion cells. It was shown that all the enhancers released completely from the adhesives and followed a square root of time kinetic (Higuchi law). Using a statistical analysis it was shown that the release rate was more dependent on the type of enhancer than on the type of polymers. The mean release rates were in the range from 2.2 to 11.1%/ radical t for the slowest and fastest releasing enhancers, which correspond to a 50% release within 500 and 20 min, respectively. Furthermore, the release rates were inversely proportional to the cube root of the molal volumes of the enhancers and to their logarithmic partition coefficients between the polymer adhesive and the receptor fluid. It was found that the observed release rates were probably due to a high diffusion coefficient of the enhancers rather than due to an inhomogeneous embedment of the enhancers in the adhesives. The type of adhesive showed minor influence on the release rate, especially among the acrylic polymers no difference was seen. However, compared to the acrylic adhesives, the polyisobutylene adhesive showed slower release rates, while the silicone adhesive showed slightly faster release rates.
Qvist
Michael H
MH
Pharmacia & Upjohn Hillerød AS, Pharmaceutical Research, Herredsvejen 2, DK-3400, Hillerod, Denmark. michael@qvist.net
Hoeck
Ulla
U
Kreilgaard
Bo
B
Madsen
Flemming
F
Frokjaer
Sven
S
D000269:Adhesives; D000279:Administration, Cutaneous; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D010599:Pharmacokinetics; D011108:Polymers; D012995:Solubility; D013329:Structure-Activity Relationship
D000269:Adhesives; D011108:Polymers