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姓名	王鑫暐(Shin-Wei Wang)  查詢紙本館藏	畢業系所	化學工程與材料工程學系
論文名稱	原料藥與水楊酸衍生物於超臨界二氧化碳中之溶解度量測 (Solubility of Pharmaceutical Compounds and Derivatives of Salicylic Acid in Supercritical Carbon Dioxide)
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檔案	[Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 (2025-6-30以後開放)
摘要(中)	本研究利用一套經可靠性驗證過之高壓相平衡半流動式裝置，搭配可見光光譜儀分析法，量測抗第二型糖尿病藥物、抗高血壓藥物與水楊酸衍生物於超臨界二氧化碳中之溶解度。所選擇之原料藥(active pharmaceutical ingredients, APIs)為格列齊特(gliclazide, GLZ)與卡托普利(captopril, CAP)，其目標藥物屬於硫醯基尿素類衍生物和脯胺酸類衍生物，前者作用為促進胰臟β細胞分泌胰島素達到降低血糖的效果；後者利用阻斷轉化酶的作用使血管得到適當的擴張。5-甲基水楊酸(5-methylsalicylic acid, 5-MSA)則屬於水楊酸之衍生物，具有影響表面活性離子溶液的團聚行為，也可應用於自我修復凝膠材料的改質。量測溫度為308.2 K、318.2 K與328.2 K，每組固定溫度下，於90 bar ~ 185 bar測量6個壓力點，一共獲得54個實驗數據點。並且於每一實驗溫度與壓力下，至少重複量測三次以上溶解度數據，其變異係數大多小於6%，其飽和溶解度之取樣流速均控制在3 L/hr ~ 10 L/hr，所量測之格列齊特、卡托普利與5-甲基水楊酸的溶解度莫耳分率範圍分別落在10-7 ~ 10-6、10-6 ~ 10-5與10-5 ~ 10-4。除了以實驗量測固體溶解度數據外，本實驗溶解度數據也使用三種密度關聯之半經驗式進行數據迴歸，包括：以結合律(association law)為基礎的Chrastil model、由稀薄溶液理論(theory of dilute solutions)的Mendez-Santiago and Teja model及多參數的Belghait model進行迴歸計算，皆能得到合理的迴歸結果，其平均相對標準誤差(average absolute relative deviation, AARD)約為1.94% ~ 8.56%。本研究也利用Chrastil model和Mendez-Santiago and Teja model作為溶解度數據的自身一致性檢測，用以驗證實驗量測數據之可靠性。
摘要(英)	In this study, a reliable high-pressure semi-flow apparatus was used to measure the solubility of antidiabetic drug, antihypertension drug and 5-methylsalicylic acid (5-MSA) in supercritical carbon dioxide (ScCO2). The active pharmaceutical ingredients (APIs) selected were gliclazide (GLZ) and captopril (CAP). The first target drug, GLZ, is a sulfonylurea derivative and acting as an antidiabetic drug. GLZ can promote the secretion of insulin from pancreatic β cells to reduce blood glucose. The second target drug, CAP, is an angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension. 5-MSA can affect the agglomeration behavior of surface active ionic liquid. Moreover, 5-MSA is also applied on material modification such as self-healing materials. The solubility of GLZ, CAP and 5-MSA in ScCO2 have been measured at 308.2 K, 318.2 K and 328.2 K and in the pressure range of 90 bar to 185 bar. The solubility data at a given temperature and pressure are repeatedly measured at least three times with different flow rates between 3 L/hr to 10 L/hr. The coefficient of variation of these repeated measurement is lower than 6%. It was found that the solubility of GLZ, CAP and 5-MSA are within the range of 10-7 to 10-6, 10-6 to 10-5 and 10-5 to 10-4, respectively. These solubility data also correlated by three semi-empirical models, including Chrastil model, Mendez-Santiago and Teja model (MST model) and Belghait model. The results of correlation with the average absolute relative deviation (AARD) are 1.94% ~ 8.56%. The self-consistency tests of the experimental data were confirmed through the Chrastil model and MST model.
關鍵字(中)	★ 超臨界二氧化碳 ★ 固體溶解度 ★ 格列齊特 ★ 卡托普利 ★ 5-甲基水楊酸	關鍵字(英)	★ Supercritical carbon dioxide ★ Solid solute solubility ★ Gliclazide ★ Captopril ★ 5-Methylsalicylic acid
論文目次	中文摘要 i Abstract ii 誌謝 iii 目錄 iv 圖目錄 vi 表目錄 ix 第一章 緒論 1 1-1 超臨界流體性質簡介 1 1-2 超臨界流體之應用 7 1-3 固體溶質於超臨界二氧化碳中之溶解度重要性 8 1-4 實驗量測固體溶質於超臨界流體中之溶解度 10 1-5 抗糖尿病藥物與抗高血壓藥物之簡介 13 1-6 研究動機 18 第二章 固體溶質於超臨界二氧化碳中之溶解度量測 20 2-1 實驗方法 20 2-1-1 實驗藥品 20 2-1-2 實驗裝置 24 2-2 實驗操作程序 28 2-2-1 半流動式裝置操作與流程 28 2-2-2 樣品成分分析與檢量線標準液配製 30 2-3 取樣流速對於固體溶質溶解度之影響 32 2-4 溶解度數據處理 35 2-5 溶解度數據迴歸 41 2-6 半經驗式模型 42 2-6-1 Chrastil model 42 2-6-2 Mendez-Santiago and Teja model 43 2-6-3 Belghait model 43 2-7 溶解度數據自身一致性測試 44 第三章 結果與討論 45 3-1 目標固體溶質之檢量線擬合 45 3-2 固體溶質之溶解度數據 49 3-3 固體溶質之半經驗式迴歸 64 3-4 固體溶質之自身一致性檢測 68 3-5 5-甲基水楊酸與甲基水楊酸異構物之溶解度比較 72 第四章 結論 74 參考文獻 75
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指導教授	謝介銘(Chieh-Ming Hsieh)	審核日期	2020-7-28
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