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KMID : 0385020030190030142
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Korean Journal of Laboratory Animal Science
2003 Volume.19 No. 3 p.142 ~ p.152
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Skin Irritation and Recrystallization Profiles of a Transdermal Patch Composed of Physostigmine and Procyclidine for the Prophylaxis of Organophosphate Poisoning
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Kim Yun-Bae
Phi Taek-San
Kim Wang-Soo
Cho Young
Seo Won-Jun
Choi Seung-Ju
Cheon Ki-Cheol
Hur Gyeung-Haeng
Yeon Gyu-Baek
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Abstract
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Skin irritation potencies of novel combinational transdermal patches, composed of various concentrations of physostigmine and procyclidine for the prophylaxis of organophosphate poisoning, were investigated in rabbits and human volunteers. In rabbits, procyclidine, but not 2.5% physostigmine, induced skin erythema in concentration- and attachment duration-dependent manners, in which moderate to severe redness was produced by attachment with patches containing 8% or higher concentrations of procyclidine over 3 days, although skin lesions including edema was not induced by patches containing procyclidine up to 10%. Interestingly, the erythemata caused by procyclidine were reduced by combination with physostigmine, and further by hydrocortisone, and the reactions were rapidly disappeared following detachment of the patches. The skin reactions induced by combinational patches in men were much similar to those in rabbits, although slight and transient edema, itching and pain were induced by patches containing 10% procyclidine. Whereas, patches containing procyclidine up to 6% in combination with physostigmine (1.5%) in the presence of hydrocortisone induced negligible redness, leading to scores lower than 1.0. Separately, only patches with a high concentration (10%) of procyclidine recrystallized from 3 weeks of storage at 4oC and 23oC, but not at 37oC, reaching 96% after 25 weeks, although the recrystallization rate was greatly lowered by addition of hydrocortisone. Based on the skin irritation and recrystallization profiles, in addition to previous skin penetration and blood concentration analyses, we selected a combinational patch containing 1.5% physostigmine + 6% procyclidine + 0.5% hydrocortisone as a transient composition for the follow-up non-clinical toxicity studies.
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KEYWORD
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Transdermal patch, Physostigmine, Procyclidine, Organophosphate poisoning, Skin irritation, recrystallization
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