Effects of ethylcellulose and 2-octyldodecanol additives on skin permeation and irritation with ethylene-vinyl acetate copolymer matrix patches containing formoterol fumarate
Effects of ethylcellulose and 2-octyldodecanol additives on skin permeation and irritation with ethylene-vinyl acetate copolymer matrix patches containing formoterol fumarate
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DOI：
10.1248/bpb.29.1717
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发表时间：
2006-08-01
影响因子：
2
通讯作者：
Takayama, Kozo
中科院分区：
文献类型：
--
作者：
Kakubari, Ikuhiro;Sasaki, Hiroyuki;Takayama, Kozo
分别使用体外大鼠和人类皮肤以及不同种类的实验动物研究了富马酸福莫特罗 (FIT) 的皮肤渗透性和乙烯-醋酸乙烯酯 (EVA) 共聚物基质贴剂的刺激性。在不添加乙基纤维素 (EC) 的情况下，FIT 的皮肤渗透性显着增加，并且通过加入 2-辛基十二烷醇 (OD) 代替氢化松香甘油酯 (Ester Gum H)，FIT 的皮肤渗透性显着增强。带有 EVA 基质贴片的 FF 对大鼠和人类皮肤渗透性的影响相似，但 24 小时后，大鼠皮肤的渗透性是人类皮肤的 1000 倍。不含 EC 和含 EC 的基质贴剂 (OD-0)、EC 和 0.5 mg OD 每平方厘米 (OD-0.5)、EC 和 1.0 mg OD 每平方厘米 (OD-1) 的主要刺激指数分别为 1.46、1.13、1.29 和 1.38。结果表明，这些贴片引起的刺激相当轻微，但明显高于对照组观察到的 0.21。单独使用 EC 或 OD 均未发现显着影响。观察到EVA基质贴剂对皮肤的刺激强度依次为兔子、豚鼠、大鼠和小型猪。
Skin permeation of formoterol fumarate (FIT) 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 FIT 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.