臺灣博碩士論文加值系統

本研究以循環式超音波結晶技術，以冷卻結晶的方式，針對原料藥甲滅酸，進行再結晶研究，並擴充其溶解度資料庫。經由初步溶解度測試及文獻回顧，本研究針對甲滅酸於4種有機溶劑，包括丁酮、甲醇、四氫呋喃、乙腈之溶解度進行測量，測量溫度範圍介於278.2K至328.2K，並利用Vant Hoff方程式對測得溶解度數據進行回歸計算。而在循環式超音波冷卻結晶研究方面，由文獻及本研究測得之溶解度數據，選擇乙酸乙酯、甲醇、乙醇、丙酮與丁酮5種溶劑進行溶劑效應的探討，再選擇結果較佳之乙酸乙酯作為溶劑系統，探討其他操作參數，包含溶液濃度、超音波強度、溶液流速與冷卻速率對生成甲滅酸微粒粒徑之影響。發現在適當的濃度、適當的超音波強度、高的溶液流速及高的冷卻速率操作下，可以得到較小的平均粒徑。在物性分析方面，原始藥物粒徑分布較廣，平均粒徑約為36 μm，經超音波處理後，粒徑較集中並可得到平均粒徑為15 μm之甲滅酸微粒。再藉由SEM、XRD、DSC、TGA與FTIR等儀器分析經循環式超音波冷卻結晶處理前後藥物微粒之物性。結果其晶體外觀較規則，固態物性維持一致，沒有分解、變質或晶型轉換的情形發生。

In the study, cooling sonocrystallization process was used to recrystallize an active pharmaceutical ingredient (API), mafenamic acid. Prior to crystallization study, solid solubilities of mafenamic acid in four organic solvents including methyl ethyl ketone, methanol,acetonitrile, and tetrahydrofuran at 278.2 K to 328.2 K were measured and correlated. In cooling sonocrystallziation, solvent effect was firstly invistagated and ethyl acetate is selected as an appropriate solvent system to further study the effects of solution concentration, sonicated intensity, solution flow rate, and cooling rate. At optimizing condition, mafenamic acid crystals with mean size of 15 μm were obtained from its original 36 μm. Furthermore the physical and chemical properties is analyzed by scanning electron microscope (SEM), X-ray powder diffraction, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA),and these properties are unchanged .

摘要 i
Abstract ii
誌謝 iv
目錄 v
表目錄 vi
圖目錄 vii
第一章 緒論 1
1.1超音波應用與介紹 1
1.2超音波藥物結晶技術文獻回顧 2
1.3目標藥物 4
1.4 研究規劃 5
第二章 實驗方法 9
2.1實驗用藥品與溶劑 9
2.2溶解度量測 9
2.3 超音波結晶實驗裝置 11
2.4操作步驟 12
2.5分析方法 13
第三章 結果與討論 20
3.1甲滅酸之溶解度量測 20
3.2甲滅酸超音波冷卻結晶 22
第四章結論 48
參考文獻 49

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