A METHOD FOR ASSESSING PERCUTANEOUS PERMEABILITY BY USING MODEL LIPIDS OF STRATUM CORNEUM

KAI Toshiya, SATO Makoto, NAKAZONO Masayuki, KUROSAKI Yuji, NAKAYAMA Taiji, KIMURA Toshikiro

doi:10.2133/dmpk.9.supplement_82

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Other Title

皮膚の薬物透過障壁の解析と角質層モデル混合脂質を用いた透過性評価法
行政&BMMC 民間開発建設技術の技術審査・証明事業における審査証明技術「ソフトコアリング」の活用について
ギョウセイ BMMC ミンカンカイハツケンセツギジュツノギジュツシンサショウメイジギョウニオケルシンサショウメイギジュツソフトコアリングノカツヨウニツイテ

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Description

The maximum fluxes (Jmax) of six β-blockers across keratinized membranes were determined in vitro and compared with their melting points (mp). Rat abdominal skin and hamster cheek pouch mucosa were used as the model membranes. Linear relations of Jmax with mp were observed in both membrane. Permeation studies using the delipidized membranes and the isolated stratum corneum (SC) sheet of hamster cheek pouch clarified that the primary rate-limiting barrier function exists in the SC especially in the intercellular lipid. A lipid mixture system (ceramide : cholesterol : palmitic acid : cholesterol-3-sulfate = 40 : 25 : 25 : 10 by weight, a mimic of intercellular lipids of SC) was used as a lipid-coated membrane and liposomes to evaluate drug permeation through the SC. The Jmax values obtained in the lipid-coated membrane, which showed linear relations with those determined in rat skin and in hamster cheek pouch, correlated with the degree of drug partition to the liposomes prepared with the same model lipid mixture, suggesting the validity of this model lipid mixture system as an in vitro system substituted for animal skin in percutaneous drug permeation studies. The usefulness of the system in assessing the penetration enhancers which act on the lipids in the SC, such as oleic acid (OA), was also clarified.

Journal

Drug Metabolism and Pharmacokinetics

Drug Metabolism and Pharmacokinetics 9 (supplement), 82-85, 1994

The Japanese Society for the Study of Xenobiotics

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