Effects of ethylcellulose and 2-octyldodecanol additives on skin permeation and irritation with ethylene-vinyl acetate copolymer matrix patches containing formoterol fumarate.
Skin permeation of formoterol fumarate (FF) and irritation with ethylene-vinyl acetate (EVA) copolymer matrix patches was investigated using rat and human skin in vitro and different species of experimental animal, respectively. Skin permeation of FF increased remarkably without addition of ethylcellulose (EC) and was remarkably enhanced by incorporation of 2-octyldodecanol (OD) instead of hydrogenated rosin glycerol ester (Ester Gum H). Effects on skin permeation of FF with EVA matrix patches were similar in rat and human skin, but rat skin was 1000 times more permeable than human skin after 24 h. The primary irritation indices for matrix patches without EC and with EC (OD-0), EC and 0.5 mg OD per square centimeter (OD-0.5), and EC and 1.0 mg OD per square centimeter (OD-1) were 1.46, 1.13,1.29 and 1.38. The results suggested that the irritation induced by these patches was rather mild, but significantly greater than the 0.21 observed with the control. No significant effects were noted for either EC or OD alone. Skin irritation intensity with EVA matrix patches was observed to be in the order of rabbits, guinea pigs, rats and miniature swine.
Kakubari
Ikuhiro
I
Research Department, Saitama Daiichi Pharmaceutical Co., Ltd, Japan. Kakubari@sdsk.co.jp
Sasaki
Hiroyuki
H
Takayasu
Toshiyuki
T
Yamauchi
Hitoshi
H
Takayama
Satoshi
S
Takayama
Kozo
K
D000279:Administration, Cutaneous; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D005030:Ethylenes / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects*; D014753:Vinyl Compounds / Q000494:pharmacology*
D004983:Ethanolamines; D005030:Ethylenes; D005233:Fatty Alcohols; D014753:Vinyl Compounds; C456972:octyl dodecanol; C013517:ethyl cellulose; D002482:Cellulose; C036216:ethylene; C011566:vinyl acetate; D000068759:Formoterol Fumarate