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Enhanced Skin Permeation of a New Capsaicin Derivative (DA-5018) from a Binary Vehicle System Composed of Isopropyl-myristate and Ethoxydiglycol
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  • Enhanced Skin Permeation of a New Capsaicin Derivative (DA-5018) from a Binary Vehicle System Composed of Isopropyl-myristate and Ethoxydiglycol
  • Enhanced Skin Permeation of a New Capsaicin Derivative (DA-5018) from a Binary Vehicle System Composed of Isopropyl-myristate and Ethoxydiglycol
저자명
Cha. Bong-Jin,Lee. Eung-Doo,Kim. Won-Bae,Chung. Suk-Jae,Lee. Min-Hwa,Shim. Chang-Koo
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2001년|24권 3호|pp.224-228 (5 pages)
발행정보
대한약학회
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정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
서지반출

기타언어초록

DA-5018, a recently synthesized capsaicin analog, appears to possess potent analgesic activity when administered topically. The objective of this study is to test the feasibility of the topical administration of this compound. Specifically, our goal was to identify vehicle system that permit a reasonable transdermal permeation of the compound in mice. Among the vehicles examined, isopropyl myristate (IPM) showed the largest in vitro permeability across the intact skin (83.6 ${pm}$ 5.42${mu}$l/$ extrm{cm}^2$/h ). However, due to the limited solubility of DA-5018 in IPM (0.53 mg/ml), the maximal flux from the IPM medium remained at only 44.3 ${pm}2.87{mu}$g/$ extrm{cm}^2$/hr. In order to increase the flux, addition of better solvents for DA-5018 was attempted, under the assumption that flux is the result of both solubility and permeability. Ethoxydiglycol (EG) and oleic acid (OA) were selected as examples of food solvents. The addition of IC or OA to IPM at a 1:1 volume ratio resulted in a comparable increase in the solubility of the compound (i.e., to 61.1 and 50.2 mg/ml for EG and OA, respectively). However, the addition of EG at a 1:1 volume ratio, for example, increased the flux 6.3 fold (i.e., $279{mu}$g/$ extrm{cm}^2$/hr), while OA, at a 1:1 volume ratio, decreased the flux 5 fold (i.e., $9.26{mu}$g/$ extrm{cm}^2$//hr). The mechanism of this discrepancy between EG and OA was investigated by measuring the permeabilty of DA-5018 across the stratum corneum-removed skin of the mouse, under the hypothesis that the viable skin layer may serve as a barrier for the permeation of lipophilic substances such as DA 5018. The permeability of DA-5018, from the medium of EG or OA, across the viable skin differed greatly for EG ($0.41{mu}$l/$ extrm{cm}^2$/hr) and OA ($0.086{mu}$l/$ extrm{cm}^2$/hr), suggesting that a higher permeability across the viable skin layer is needed for the second solvents. The maximum flux across the intact skin was achieved for DA-5018 when EG was added to IPM at a 1:1 volume ratio. Thus, the use of a binary system appears to be the best approach for realizing the transdermal delivery of DA-5018 at a reasonable rate.