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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/4493

    標題: Fluvastatin軟膏製劑在經皮吸收之研究
    Study on the Use of Ointment Preparations for Transdermal Delivery of Fluvastatin
    作者: 王博駿
    Po-chiun Wang
    貢獻者: 林恆弘
    關鍵字: 幾丁聚醣親水性凝膠
    FAPG ointment
    UCH ointment
    Percutaneous absorption
    Permeation rate
    chitosan hydrogel
    日期: 2004
    上傳時間: 2008-10-15 17:20:59 (UTC+8)
    摘要: Fluvastatin是第一個合成產生並且允言午應用在臨床脂質調節治療的HMG-Co A(3-Hydroxy-3-Methyl-Glutaryl CoenzymeA)還元酶抑制劑。本研究中,選用軟膏劑型來進行藥物的經皮吸收。所使用的軟膏劑型包括chitosan親水凝膠、FAPG(fatty alcohol propylene glycol)與UCH(University of California Hospital)基劑,並探討基劑組成對黏稠度跟藥物釋離的影響。首先在軟膏的物化特性方面,是使用Cone and Plate黏度計和熱卡式示差分析儀(DSC)做分析。在fluvastatin軟膏、藥物製備、軟膏之體外藥物釋放、藥物經皮吸收後的濃度和在皮膚上殘存的藥物濃度都藉由HPLC來檢測。最後使用大白鼠皮(rat)來做體外皮膚穿透實驗,探討軟膏基劑對於fluvastatin在大白鼠皮的經皮吸收的影響。結果顯示,軟膏是一種假塑性流體,且軟膏劑型的物化特性會影響fluvastatin的藥物釋放,藥物釋放速率的順序分別是chitosan base > FAPG base > UCH base。Fluvastatin的釋放速率剛好與黏稠度相反。在DSC的測定下,只有chitosan軟膏在加入了fluvastatin後不會產生交互作用。但是在其他兩種軟膏則會產生一些交互作用,而且在相同黏稠度下會抑制藥物的釋放。另外,使用界面活性劑來增加fluvastatin的經皮吸收,如benzalkonium chloride、sodium lauryl sulfate、Tween 80、Span 40。在界面活性劑中以benzalkonium chloride及sodium lauryl sulfate的透皮促進效果比Tween 80及Span 40好,使用濃度以1%為最佳,濃度超過1%反而會降低藥物穿透的效果。在皮膚藥物殘留則以UCH軟膏的殘留量>FAPG軟膏>chitosan軟膏。
    Fluvastatin is the first synthetic HMG-Co A reductase inhibitor to be approved for clinical lipid-modifying therapy. In this study, we attempt to develop a transdermal delivery system by the use of ointment dosage forms. The type of ointments include chitosan hydrogel ,FAPG, UCH. In the work, the effect of variation in the composition and preparation condition of ointments on the viscosity, adhesive of products and drug release were investigated. The physicochemical properties of ointments were determined by Cone and Plate viscometer, texture analyzer and differential scanning calorimetry. For these fluvastatin ointments, drug loading, in vitro release of drug from the ointment, drug concentration after transdermal absorption and cumulative amount of drug in skin were quantified by high performance liquid chromatography (HPLC). The effect of ointment physicochemical properties on the release of fluvastatin from ointment base and the percutaneous penetration through rat skin were discussed by in vitro studies. In the in vitro studies, we investigated the effect of ointments composition on the transdermal delivery of fluvastatin in rats. The results indicated that ointments are referred to as pseudoplastic flow and the increase in the drug release rate for the ointments conformed to the following order: chitosan base > FAPG base > UCH base. The release rate of fluvastatin was inversely proportional to ointment viscosity. By differential scanning calorimetry (DSC) measurement, no interaction was found to occur between chitosan ointment base and the soluble fluvastatin. But some kind of interaction between the other ointment bases and the incorporated drug may suppress the drug release rate in the same viscosity level. Surfactants such as benzalkonium chloride, sodium lauryl sulfate, Tween 80 and Span 40 were used as penetration enhancers to increase the percutaneous absorption of fluvastatin. Among the surfactants, the penetration efficiency of benzalkonium chloride and sodium lauryl sulfate were better than Tween 80 and Span 40. The concentration 1% of enhancer was found to be most efficient. Additionally, the drug retention in the rat skin of various ointment bases were increased in the order UCH base> FAPG base> chitosan base.
    關聯: 校內校外均不公開
    Appears in Collections:[生物科技系(所)] 博碩士論文

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