| 摘要: | 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。;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. |
