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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/44590完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳延平(Yan-Ping Chen) | |
| dc.contributor.author | Yen-Ming Chen | en |
| dc.contributor.author | 陳彥銘 | zh_TW |
| dc.date.accessioned | 2021-06-15T03:51:28Z | - |
| dc.date.available | 2012-07-15 | |
| dc.date.copyright | 2010-07-15 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-07-13 | |
| dc.identifier.citation | Abramoff, M. D., Magelhaes, P .J. and Ram, S. J., Image processing with ImageJ, Biophotonics Int., 11 (2004) 36-42
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E., Measurements of solid solubilities and volumetric properties of naphthalene + carbon dioxide mixtures with a new assembly taking advantage of a vibrating tube densitometer, Fluid Phase Equilibria, 234 (2005) 151-163 鄭光煒，超臨界二氧化碳中之相平衡測量及固體溶解度計算，國立台灣大學化學工程學研究所博士論文，2002 鄭肇心，無限稀薄活性係數模式之改良及應用，國立台灣大學化學工程學研究所博士論文，2003 蘇至善，藥物固體於超臨界二氧化碳中溶解度與微粒化之硏究，國立台灣大學化學工程學研究所博士論文，2007 黃世岳，固體乙醯苯胺類物質於超臨界二氧化碳中溶解度之實驗量測與關聯，國立台灣大學化學工程學研究所研究所碩士論文，2003 蘇至善，以批式超臨界反溶劑沉積法進行非類固醇抗發炎藥之再結晶研究，國立台灣大學化學工程學研究所碩士論文，2003 張雲評，以超臨界反溶劑沉積法進行藥物微粒化之研究，國立台灣大學化學工程學研究所碩士論文，2005 陳鈞振，以連續式超臨界反溶劑沉積法進行藥物微粒化及包覆之研究，國立台灣大學化學工程學研究所碩士論文，2006 林柏青，利用超臨界快速膨脹法進行Gemfibrozil、Lidocaine、Ethosuximide及Tolbutamide藥物微粒化之研究，國立台灣大學化學工程學研究所碩士論文，2008 蔡豐年，利用連續式超臨界反溶劑法處理原料藥：Sulfamerazine and Acetazolamide，國立台灣大學化學工程學研究所碩士論文，2008 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/44590 | - |
| dc.description.abstract | 本研究主要是針對藥物於超臨界二氧化碳中之固體溶解度，進行實驗量測與使用理論模式進行廻歸計算，最後以超臨界溶液快速膨脹法 (RESS) 與超臨界反溶劑法 (SAS) 對藥物進行再結晶與微粒化研究。
在固體溶解度實驗量測方面，本研究建立一半流動式量測設備，搭配使用HPLC的非線上分析方法，選擇3種非類固醇抗發炎藥，分別為antipyrine、4-aminoantipyrine與4-dimethylaminoantipyrine；與3種降血脂劑，分別為clofibric acid、fenofibrate與gemfibrozil，進行其於超臨界二氧化碳中之固體溶解度量測。量測溫度為308.2、318.2與328.2 K，每個固定溫度下，於10~22 MPa之間各7個量測壓力，共得到126個實驗數據點。並使用MST、Chrastil與Bartle等3種半經驗模式，針對溶解度實驗數據進行廻歸計算，發現皆能得到良好的計算結果。 對於固體於超臨界二氧化碳中溶解度之理論廻歸計算而言，本研究依照固體結構式或依照藥物功能性，將計算系統分類為9種，分別為酚環類固體、萘類固體、非類固醇抗發炎藥、降血脂劑、類固醇藥、磺胺藥、維生素、抗氧化劑與染料，共91種固體溶質於超臨界二氧化碳中的溶解度數據，總共2158個實驗數據點。並將與超臨界密度相關之溶液模式進行無因次化的修正，利用其來進行溶解度數據廻歸計算，最後將參數進行簡化與關聯，發現經由將參數與相對應的固體溶質熱力學性質進行關聯所得到的預測模式，皆能有效且合理的預測固體溶解度行為。而利用單一實驗數據點之調整來預測溶解度行為之方法，更能提升預測之效能，在僅需要單一數據點的要求下，即可對固體溶解度行為進行有效的描述。 在研究的最後兩部分中，本研究首先建立一超臨界溶液快速膨脹法微粒化設備，將降血脂劑fenofibrate之平均粒徑由原始的19.50減小至3.94 μm，同時也成功的利用RESOLV程序，將藥物經由噴嘴噴入一水溶液的環境中，製備成穩定的微粒懸浮液，微粒化後之平均粒徑可再減小至2.02 μm。而經由微粒化後，藥物的多晶型態並沒有造成改變。且經超臨界反溶劑法處理後的藥物微粒，其溶離速率有顯著的提升，最高可比原始藥物快2.95倍。除此之外，本研究接著建立一半連續式超臨界反溶劑法微粒化設備，將磺胺藥sulfathiazole之平均粒徑由原始的42.99減小至2.07 μm。而經由微粒化後，在使用丙酮為溶劑時，藥物多晶型態可由原始的晶型Form III轉變成晶型Form I，而在使用乙醇為溶劑時，則轉變成晶型Form IV。同樣的，經超臨界反溶劑法處理後的藥物微粒，其溶離速率亦有顯著的提升，最高可比原始藥物快3.19倍。 | zh_TW |
| dc.description.abstract | In this study, measurement and correlation of solid solubility for active pharmaceutical ingredients (APIs) and organic compounds in supercritical carbon dioxide were investigated. And re-crystallization and micronization for APIs were also investigated using rapid expansion of supercritical solution (RESS) and supercritical anti-solvent (SAS) processes.
The solid solubilities of three non-steroidal anti-inflammatory drugs (NSAIDs) of antipyrine, 4-aminoantipyrine, 4-dimethylaminoantipyrine, and three antilipemic agents of clofibric acid, fenofibrate, gemfibrozil in supercritical carbon dioxide were measured using a semi-flow apparatus. Total 126 data points were obtained. These experimental results were correlated by three semi-empirical models of Mendez-Santiago-Teja, Chrastil and Bartle. The measured data satisfied the self-consistency test, and the parameters in the semi-empirical models are feasible for data extrapolation. Beside the solubility measurement, the solubility data for nine families of phenolic compounds, naphthalene compounds, nsaids, antilipemic agents, steroids, sulfonamids, vitamins, antioxidant agents and dyes, totally 91 compounds and 2158 data points, were correlated using the solution model in its dimensionless form. This correlation can further be generalized to predict the solubility of complex solid in supercritical carbon dioxide. Furthermore, prediction of the solubility using only single data point was available. The solution model with less parameters yielded comparably satisfactory results to those from commonly used semi-empirical models. The unique prediction ability of the solution model is also demonstrated. Re-crystallization and micronization for an antilipemic agent fenofibrate were investigated using rapid expansion of supercritical solution (RESS) process. The mean particle size of fenofibrate was reduced from its original 19.50 to 3.94 μm under the optimal operation conditions. We also using RESOLV process to formation the fenofibrate particles in aqueous suspension. The mean particle size was further reduced to 2.02 μm after RESOLV treated under the optimal operation conditions. It presented an enhanced dissolution rate for fenofibrate in a simulated gastric fluid that was 2.95 times than the original compound. Finally, re-crystallization and micronization for a sulfonamid sulfathiazole were investigated using semi-continuous supercritical anti-solvent (SAS) process. The mean particle size of sulfathiazole was reduced from its original 42.99 to 2.07 μm under the optimal operation conditions. It was observed that different kinds of solvents resulted in different polymorphisms. The original sulfathiazole had the Form III crystalline. It was re-crystallized and micronized into Form I when acetone was used as the solvent in SAS process. The polymorph changed to Form IV when ethanol was used as the solvents. It also presented an enhanced dissolution rate for sulfathiazle in a simulated intestinal fluid that was 3.19 times than the original compound. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T03:51:28Z (GMT). No. of bitstreams: 1 ntu-99-F94524049-1.pdf: 4106256 bytes, checksum: 2fcf469d36de7bd8f01848a37408bb15 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 中文摘要 I
英文摘要 III 目錄 V 表目錄 VII 圖目錄 XI 第一章 緒論 1-1 超臨界流體之介紹與應用發展 1 1-2 熱力學性質研究之重要性 3 1-3 藥物微粒化與多晶型之重要性 4 1-4 超臨界流體微粒製備技術介紹 7 1-5 研究規劃 11 第二章 藥物固體於超臨界二氧化碳中之溶解度實驗量測 2-1 研究背景與動機 17 2-2 實驗方法 21 2-3 應用熱力學模式計算固體溶解度 27 2-4 實驗用藥品 29 2-5 實驗結果與討論 29 2-6 結論 32 第三章 利用活性係數模式計算固體溶質於超臨界二氧化碳中之溶解度 3-1 研究背景與動機 62 3-2 計算方法 65 3-3 計算用系統 70 3-4 計算結果與討論 71 3-5 結論 89 第四章 利用超臨界溶液快速膨脹法進行藥物再結晶與微粒化研究 4-1 研究背景與動機 152 4-2 實驗方法 155 4-3 分析方法 159 4-4 實驗用藥品 165 4-5 實驗結果與討論 165 4-6 結論 171 第五章 利用超臨界反溶劑法進行藥物再結晶與微粒化研究 5-1 研究背景與動機 186 5-2 實驗方法 190 5-3 分析方法 193 5-4 實驗用藥品 194 5-5 實驗結果與討論 194 5-6 結論 200 第六章 結論 214 符號說明 216 參考文獻 219 附錄 236 作者簡介 252 | |
| dc.language.iso | zh-TW | |
| dc.title | 應用超臨界二氧化碳於藥物分子溶解度與微粒化之研究 | zh_TW |
| dc.title | Application of Supercritical Carbon Dioxide on Solubility and Micronization of Pharmaceutical Compounds | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 林河木,陳立仁,李夢輝,林祥泰 | |
| dc.subject.keyword | 超臨界流體,溶解度,微粒化, | zh_TW |
| dc.subject.keyword | supercritical fluid,solubility,micronization, | en |
| dc.relation.page | 254 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-07-13 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 化學工程學研究所 | zh_TW |
| 顯示於系所單位： | 化學工程學系 | |
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