Cutaneous effects of transdermal levonorgestrel.
The irritation of transdermal devices delivering levonorgestrel and the permeation enhancer ethyl acetate with or without ethanol was evaluated in rabbits. Erythema and oedema were assessed 24, 48 and 72 hr and 7 days after application of the 24-hr delivery system. The devices were found to be mild to moderately irritating, with erythema the primary manifestation. No differences were observed between devices using pure ethyl acetate or ethyl acetate-ethanol (7:3, v/v) as enhancers. Devices using pure ethanol as an enhancer gave levels of irritation similar to those using ethyl acetate-ethanol (7:3) or pure ethyl acetate. Control devices containing only water (no drug) were also found to be mildly irritating to rabbits following a 24-hr exposure period. A histological evaluation of the application sites of two of the formulations confirmed the visual observations of mild subacute irritation. The changes produced by transdermal levonorgestrel were reversible. The problems of skin irritation of transdermal devices is discussed with particular reference to the use of ethyl acetate and ethanol as skin penetration enhancers.
Friend
D R
DR
Controlled Release and Biomedical Polymers Department, SRI International, Menlo Park, CA 94025.
Phillips
S J
SJ
Hill
J R
JR
D000085:Acetates / Q000633:toxicity; D000279:Administration, Cutaneous; D000818:Animals; D004890:Erythema / Q000139:chemically induced; D000431:Ethanol / Q000633:toxicity; D005260:Female; D007509:Irritants / Q000633:toxicity; D016912:Levonorgestrel / Q000633:toxicity*; D010328:Patch Tests; D011817:Rabbits; D012867:Skin / Q000187:drug effects* / Q000473:pathology
D000085:Acetates; D007509:Irritants; D000431:Ethanol; D016912:Levonorgestrel; C007650:ethyl acetate