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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/21725


    標題: The delivery and antinociceptive effects of morphine and its ester prodrugs from lipid emulsions
    作者: Jhi-Joung Wang
    K.C. Sung
    Chih-Hui Yeh
    Jia-You Fang
    貢獻者: 藥物科技研究所
    關鍵字: Morphine
    Prodrugs
    Lipid emulsions
    Drug delivery
    Phosphatidylethanolamine
    日期: 2008-04
    上傳時間: 2009-10-13 09:29:27 (UTC+8)
    摘要: Long-acting analgesia is critical for patients suffering from long-acting pain. The purpose of this study was to develop lipid emulsions as parenteral drug delivery systems for morphine and its ester prodrugs. Morphine prodrugs with various alkyl chain lengths, including morphine propionate (MPR), morphine enanthate (MEN), and morphine decanoate (MDE), were synthesized. The prodrugs were stable against chemical hydrolysis in an aqueous solution, but were quickly hydrolyzed to the parent drug when exposed to esterase and plasma. Lipid emulsions were prepared using phosphatidylethanolamine (PE) as an emulsifier, while squalene was used as an inner oil phase. Drug release was found to be a function of the drug/prodrug lipophilicity, with a lower release rate for more-lipophilic drug/prodrugs. The inclusion of morphine and its prodrugs into lipid emulsions retarded their release. Lipid emulsions, which incorporated cholesterol, generally exhibited a drug/prodrug release comparable to that of emulsions without co-emulsifiers. Pluronic F68 (PF68) further slowed down the release of morphine and its prodrugs from the emulsions. The antinociceptive activity through the parenteral administration of these emulsions was examined using a cold ethanol tail-flick study. Compared with an aqueous solution, a prolonged analgesic duration was detected after application of the drug/prodrug emulsions. Incorporation of co-emulsifiers such as PF68 and cholesterol further increased the duration of action. The combination of prodrug strategy and lipid emulsions may be practically useful for improving analgesic therapy with morphine.
    關聯: International Journal of Pharmaceutics 353(1-2):p.95-104
    Appears in Collections:[藥學系(所)] 期刊論文

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