請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33154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 | Jiun-Jen Chen | en |
| dc.contributor.author | 陳鈞振 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:27:05Z | - |
| dc.date.available | 2006-07-25 | |
| dc.date.copyright | 2006-07-25 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-20 | |
| dc.identifier.citation | Abramoff, M.D., Magelhaes, P.J., Ram, S.J., Image processing with ImageJ, Biophotonics Inter., 11, 2004, 36-42
Burgos-Solórzano, G.I., Brennecke, J.F., Stadtherr, M.A., Solubility measurements and modeling of molecules of biological and pharmaceutical interest with supercritical CO2, Fluid Phase Equilibria, 220, 2004, 57–69 Carretier, E., Badens, E., Guichardon, P., Boutin, O., Charbit, G., Hydrodynamics of supercritical antisolvent precipitation: characterization and influence on particle morphology, Ind. Eng. Chem. Res, 42, 2003, 331-338 Calderone, M., Rodier, E., Freiss, B., Letourneau, J.J., and Fages, J., Coating of nanoparicles using a supercritical antisolvent(SAS) process, 7th Italian Conference on Supercritical Fluids and Their Applications, Italy, 2004 Chattopadhyay, P. and Gupta, R., Production of griseofulvin nanoparticles using supercritical CO2 antisolvent with enhanced mass transfer, Inter. J. Pharm., 228, 2001, 19-31 Chen, K., Zhang, X., Panb, J., Zhang, W. and Yinc, W., Gas antisolvent precipitation of Ginkgo ginkgolides with supercritical CO2, Powder Tech., 152, 2005, 127-132 Cocero, M.J. and Ferrero, S., Crystallization of β-Carotene by a GAS process in batch effect of operating conditions, J. Supercrit. Fluids, 22, 2002, 237-245 Craig, D., Royall, P., Kett, V. and Hopton, L., The relevance of the amorphous state to pharmaceutical dosage forms glassy drugs and freeze dried systems, Inter. J. Pharm., 179, 1999, 179–207 Das, K.G., Controlled release technology: bioengineering aspects, JohnWiley &Sons, New York, 1983 Domingo, C., Vega, A., Fanovich, M.A., Elvira, C., Subra P., Behavior of poly(methyl methacrylate)-based systems in supercritical CO2 and CO2 plus cosolvent: solubility measurements and process assessment, J. Appl. Polym. Sci., 90, 2003, 3652-3659 Edwards, A., Shekunov, B., Kordikowski, A., Forbes, R. and York, P., Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical fluids (SEDSTM). J. Pharm. Sci., 90, 2001, 1115–1124 Elvassore, N., Bertucco, A., Caliceti, P., Production of insulin-loaded poly(ethylene glycol)/Poly(l-lactide)(PEG/PLA) nanoparticles by gas antisolvent techniques, J. Pharm. Sci., 90, 2001a, 1628-1636 Elvassore, N. and Bertucco, A., Production of protein-loaded polymeric microcapsules by compressed CO2 in a mixed solvent, Ind. Eng. Chem. Res., 40, 2001b, 795-800 Elvassore, N., Vezzu, K., Bertucco, A., Cecchi, A., Caliceti, P.,Protein loading in biodegradable polymeric micro-particles produced by compressed gas antisolvent techniques, 7th Italian Conference on Supercritical Fluids and Their Applications, Italy, 2004 Elvassore, N., Parton, T., Bertucco A., Kinetics of particle formation in the gas antisolvent precipitation process, AIChE J., 49, 2003, 859-868 Falk R. and Randolph, T. W., Process variable implications for residual solvent removal and polymer morphology in the formation of gentamycin-loaded poly(l-lactide) microparticles, Pharm. Res., 15, 1998, 1233-1237 Falk, R., Randolph, T.W., Meyer, J.D., Kelly, R. M., Manning M.C., Controlled release of ionic compounds from poly(l-lactide) microspheres produced by precipitation with a compressed antisolvent, J. Controlled Release, 44, 1997, 77-85 Ferrero, C., Bravo, I., Jimenez-Castellanos, M.R., Drug release kinetics and fronts movement studies from methyl methacrylate (MMA) copolymer matrix tablets: effect of copolymer type and matrix porosity, J. Control. Rel., 92, 2003, 69-82 Foster, N., Mammucari, R., Dehghani, F., Barrett, A., Bezanehtak, K., Coen, E., Combes, G., Meure, L., Aaron N., Regtop, H. and Tandya, A., Processing pharmaceutical compounds using dense gas technology, Ind. Eng. Chem. Res, 42, 2003, 6476-6493 Galen W.E., Instrumental methods of chemical analysis,5th ed., McGraw-Hill, New York, 1985 Gioannis, B., Jestin, P., Subra, P., Morphology and growth control of griseofulvin recrystallized by compressed carbon dioxide as antisolvent, J. Crystal Growth, 262, 2004, 519-526 Haleblian, J., Characterization of habits and crystalline modification of solids and their pharmaceutical applications, J. Pharm. Sci., 64, 1975, 1269-1288 He, W.Z., Suo, Q. L. Jiang, Z. H., A, S., Hong, H.L., Precipitation of ephedrine by SEDS process using a specially designed prefilming atomizer, J. Supercrit. Fluids, 31, 2004, 101-110 Higuchi, T., Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices, J. Pharm. Sci., 52, 1963, 1145 Hong, L., Guo, J., Gao, Y. and Yuan, W.K., Precipitation of microparticulate organic pigment powders by a supercritical antisolvent process, Ind. Eng. Chem. Res., 39, 2000, 4882-4887 Juan, M.A.H., Esther, A.V.P., Jaime, H.T., Experimental and theoretical study of the conformational analysis of hydrochlorothiazide, J. Molecular Structure, 786, 2006, 1-8 Jung, J., and Perrut, M., Particle design using supercritical fluids: Literature and patent survey, J. Supercrit. Fluids, 20, 2001, 179-219 Kayrak, D., Akman, U. and Hortacsu, O., Micronization of ibuprofen by RESS, J. Supercrit. Fluids, 26, 2003, 17-31 Kerc, J., Srcic, S., Knez, Z. and Sencar-Bozic, P., Micronization of drugs using supercritical carbon dioxide, Inter. J. Pharm., 182, 1999, 33–39 Lerk, C.F., Bolink, W.J., Zuurman, K., Solid dosage form with contant release, Pharm. Ind. , 38, 1976, 561 Leon, S. and Andrew, Y., Applied biopharmaceutics and pharmacokinetics, 4th ed., 1999, McGraw-Hill Leuner, C. and Dressman, J., Improving drug solubility for oral delivery using solid dispersions, Euro. J. Pharm. Biopharm., 50, 2000, 47-60 Mosharraf, M. and Nystrom, C., The effect of particle size and shape on the surface specific dissolution rate of microsized practically insoluble drugs, Inter. J. Pharm., 122, 1995, 35–47 Moshashaee S., Bisrat, M., Forbes, R.T., Nyqvist, N. and York, P., Supercritical fluid processing of proteins：lysozyme precipitation from organic solution, Euro. J. Pharm. Sci., 11, 2000, 239-245 Muller, M., Meier, U., Kessler, A., and Mazzotti, M., Experimental study of the effect of process parameters in the recrystallization of an organic compound using compressed carbon dioxide as antisolvent, Ind. Eng. Chem. Res. , 39, 2000, 2260-2268 Perrut, M., Jung, J. and Leboeuf, F., Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes Part I:Micronization of neat particles, Inter. J. Pharm., 288, 2005, 3-10 Randolph, T.W., Randolph, A.D., Mebes, M., Yeung S., Sub-micrometer-sized biodegradable particles of poly(l-lactic acid) via the gas antisolvent spray precipitation process, Biotech. Prog., 9, 1993, 429-435 Reverchon, E., Spada A., Erythromycin micro-particles produced by supercritical fluid atomization, Powder Tech., 141, 2004a, 100-108 Reverchon, E., and De, M., Supercritical antisolvent micronization of Cefonicid：thermodynamic interpretation of results, J. Supercrit. Fluids, 31, 2004b, 207-215 Reverchon, E., Porta, G.D., Rosa, I.D., Subra, P., Letourneur, D., Supercritical antisolvent micronization of some biopolymers, J. Supercrit. Fluids, 18, 2000a, 239-245 Reverchon, E., Porta, G.D. and Falivene, M.G., Process parameters and morphology in amoxicillin micro and submicro particles generation by supercritical antisolvent precipitation, J. Supercrit. Fluids, 17, 2000b, 239-248 Reverchon, E., De, M.I., and Porta, G.D., Rifampicin microparticles production by supercritical antisolvent precipitation, Inter. J. Pharm., 243, 2002, 83-91 Reverchon, E., Porta, G.D. and Pallado, P., Supercritical antisolvent recipitation of salbutamol microparticles, Powder Tech., 114, 2001, 17-22 Shieh, L., Tamada, J., Chen, I., Pang, J., Domb, A., Langer, R., Erosion of a new family of biodegradable polyanhydrides. J. Biomed. Mater. Res., 28, 1994, 1465-1475 Snavely, W.K., Subramaniam, B., Rajewski, R.A., and Defelippis, M.R., Miconization of insulin from halogenated alcohol solution using supercritical carbon dioxide as an antisolvent, J. Pharm. Sci., 91, 2002, 2026-2039 Su, C.S., Chen Y.P., Recrystallization of salicylamide using a batch supercritical antisolvent process, Chem Eng. Technol., 28, 2005, 1177-1181 Subra, P., Berroy, P., Vega, A., Domingo, C., Process performances and characteristics of powders produced using supercritical CO2 as solvent and antisolvent, Powder Tech., 142, 2004, 13-22 Taki, S., Badens, E., Charbit, G., Controlled release system formed by supercritical anti-solvent coprecipitation of a herbicide and a biodegradable polymer, J. Supercrit. Fluids, 21, 2001, 61-70 Thiering, R., Dehghani, F. and Foster, N., Current issues relating to anti-solvent micronization techniques and their extension to industrial scales, J. Supercrit. Fluids, 21, 2001, 159-177 Thiering, R. Dehghani, F, Dillow, A and Foster, N.R., Solvent effects on the controlled dense gas precipitation of model proteins , J. Chem. Tech. and Biotech., 75, 2000, 42-53 Thiering, R., Dehghani, F., Dillow, A. and Foster, N. R., The influence of operating conditions on the dense gas precipitation of model proteins, J. Chemical Tech. and Biotech., 75, 2000, 29-41 The United States Pharmacopeia, Section：Test Solutions, 28th revision, United States Pharmacopeial Convention, Inc., Washington, D.C., 2005 Toti, Udaya, S., Aminabhavi, Tejraj, M., Modified guar gum matrix tablet for controlled release of diltiazem hydrochloride, J. Control. Rel., 95, 2004, 567-577 Tu, L.S., Dehghani, F., Foster, N.R., Micronisation and microencapsulation of pharmaceuticals using a carbon dioxide antisolvent, Powder Tech., 126, 2002, 134– 149 Ventosa, N., Sala, S. and Veciana, J., Depressurization of an expanded liquid organic solution (DELOS): a new procedure for obtaining submicron- or micron-sized crystalline particles, Crystal Growth and Design, 1, 2001, 299-303 Velaga, S., Ghaderi, R., Carlfors, J., Preparation and characterisation of hydrocortisone particles using a supercritical fluids extraction process, Inter. J. Pharm., 245, 2002, 75-82 Wagner, J.G., Interpretation of percent dissolved-time plots derived from in vitro testing of conventional tablets and capsules, J. Pharm. Sci., 58, 1969, 1253. Wang, Y., Dave, R.N., Pfeffer, R., Polymer coating / encapsulation of nanoparticles using a supercritical anti-solvent process, J. Supercrit. Fluids, 28, 2004, 85-99 Wang, Y., Pfeffer, R., and Dave R.N., Polymer encapsulation of fine particles by a supercritical antisolvent process, AIChE J., 51, 2005, 440-455 Warwick, B., Dehghani, F. and Foster, N. R., Micronization of copper indomethacin using gas antisolvent processes, Ind. Eng. Chem. Res, 8, 2002, 1993-2004 Yeo, S.D. and Lee, J.C., Crystallization of sulfamethizole using the supercritical and liquid antisolvent processes, J. Supercrit. Fluids, 30, 2004, 315-323 Young, T.J., Johnston, K.P., Mishima, K., Tanaka, H., Encapsulation of lysozyme in a biodegradable polymer by precipitation with a vapor-over-liquid antisolvent, J. Pharm. Sci., 88, 1999, 640-650 Yue, B., Yang, J., Wang, Y., Huang, C.Y., Dave, R., Pfeffer, R., Particle encapsulation with polymer via in situ polymerization, Powder Tech., 146, 2004, 32-45 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 沈宗禮，制放技術與微粒包覆，高立圖書公司，1980 傅佑璋，聚乳酸(PLA)及乳酸/羥基乙酸共聚合物(PLGA)於抗癌藥物 傳輸系統之研究，國立中央大學化學工程學研究所博士論文，2001 葉佳雯，以苯胺有機鹼催化溶膠-凝膠反應製備壓克力-二氧化矽複合材料及其性質之研究，私立中原大學化學研究所博士論文，2004 廖晏生，尿素酵素固定化醋酸纖維素中空纖維在血液透析之研究，國立台灣科技大學纖維及高分子工程研究所，1999 呂維明，戴怡德，粉粒體粒徑量測技術，高立圖書有限公司，1998 吳漢鍾，超臨界二氧化碳製備微奈米阿司匹靈膠囊粒子及控制釋放之 模擬胃液研究，國立成功大學化學工程學研究所碩士論文，2000 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33154 | - |
| dc.description.abstract | 本研究以超臨界反溶劑法(SAS)法，進行高分子及藥物微粒化，超臨界CO2扮演反溶劑的角色，使得溶液體積膨脹，溶液迅速達過飽和而析出溶質。本研究利用超臨界反溶劑法，成功地將PMMA, CA, HPC等高分子微粒化。Hydrochlorothiazide (HCT, 利尿劑), Tolazamide, Succinic acid, Naringin等藥物經過SAS操作，亦得到良好的微粒化效果。
在本研究選定利尿劑HCT進行操作參數的探討，在不同的壓力、溫度、溶液濃度、溶液流速下進行實驗，探討各參數對粒徑及晶貌的影響。研究結果顯示，在壓力為120bar，溫度為45℃，溶液濃度為10%飽和濃度及溶液流率為0.25mL/min時，可得最小的HCT粒徑為0.67µm。 本研究又以利尿劑HCT為核心藥物，生物可分解性高分子PLA為殼層物質進行包覆，並探討原始藥物、微粒化藥物及包覆後藥物的溶離速率情形。經由本研究SAS操作得到的微粒化HCT藥物之溶離速率，較原始藥物提升了3倍，而包覆後的微囊，具有延長釋放的效果，且其釋放動態模式，符合Higuchi釋放動力模式。 | zh_TW |
| dc.description.abstract | The purpose of this study was to apply the technique, supercritical anti-solvent (SAS) to the preparation of micronized polymers and drugs. In the SAS process, supercritical CO2 acts as an anti-solvent for the solution. The supercritical CO2 causes supersaturation of the solution, leading to nucleation and precipitation of the solute rapidly. The polymers such as PMMA, CA, HPC were successfully micronized using the SAS process. At the same time, the size of drugs such as Hydrochlorothiazide (HCT), Tolazamide, Succinic acid and Naringin were also greatly reduced after the SAS process.
In this research, the effect of the process parameters was discussed using HCT as model drug. The operating parameters that have an effect on the size of the drug, such as pressure, temperature, concentration of solution and flow rate of solution, were systematically studied to find the optimum operating parameters. We got the smallest average particle size, 0.67µm of HCT at the condition that P=120bar, T=45℃,solution concentration=10% sat., solution flow rate=0.25mL/min. Encapsulation of fine particles with polymer using the supercritical antisolvent coating process was also investigated in this research. The diuretic drug, HCT particles were used as host particles and PLA, a biodegradable polymer used for controlled release of drugs, was chosen as the coating material. This study also discussed the dissolution rates of original, micronized and encapsulated drugs. The dissolution rate of micronized HCT which were obtained after continuous SAS was 3 times greater than that of the original drug. The encapsulated drug allows a slow and prolonged drug release and the release profile of the encapsules matches the Higuchi matrix release kinetic model. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:27:05Z (GMT). No. of bitstreams: 1 ntu-95-R93524051-1.pdf: 9728073 bytes, checksum: 4ce6f1b4a2ffc09b045dcdb187ee9179 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 中文摘要 I
英文摘要 II 目錄 III 表目錄 V 圖目錄 VI 第一章 緒論 1 1-1超臨界流體介紹 1 1-2超臨界流體技術應用於藥物微粒化 1 1-3控制釋放 8 1-4超臨界流體技術應用於藥物包覆 10 1-5藥物微粒溶離動力學與藥物釋放動力模式 12 1-6目標藥物介紹 18 第二章 實驗方法 22 2-1 實驗裝置 22 2-2 實驗操作步驟 23 2-2-1 目標藥物可溶性之測試 23 2-2-2 連續式超臨界反溶劑沉積操作步驟 23 2-3 分析方法 25 2-3-1藥物顆粒型態與粒徑大小分析 25 2-3-2藥物結晶特性分析 26 2-3-3藥物熱效應分析 26 2-3-4藥物定性分析 27 2-3-5藥物包覆組成與有效負載率分析 27 2-4溶離速率試驗 28 2-5實驗設計 29 第三章 結果與討論 31 3-1超臨界反溶劑微粒化結果 31 3-1-1高分子微粒化之結果 31 3-1-2藥物微粒化之結果 34 3-2連續式超臨界反溶劑微粒化操作參數探討 36 3-3超臨界反溶劑包覆結果 41 3-3-1藥物包覆定性分析 41 3-3-2藥物包覆定量分析 43 3-4藥物溶離速率及釋出結果 44 第四章 結論 47 參考文獻 101 | |
| dc.language.iso | zh-TW | |
| dc.subject | 微粒化 | zh_TW |
| dc.subject | 超臨界反溶劑法 | zh_TW |
| dc.subject | 包覆 | zh_TW |
| dc.subject | Supercritical antisolvent | en |
| dc.subject | Encapsulation | en |
| dc.subject | Micronization | en |
| dc.title | 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 | zh_TW |
| dc.title | Micronization and Encapsulation of Pharmaceutical Compounds Using Supercritical Anti-Solvent Precipitation Process | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蔡偉博(Wei-Bor Tsai),胡宇方(Yu-Fang Hu) | |
| dc.subject.keyword | 微粒化,包覆,超臨界反溶劑法, | zh_TW |
| dc.subject.keyword | Micronization,Encapsulation,Supercritical antisolvent, | en |
| dc.relation.page | 109 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-22 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-95-1.pdf 未授權公開取用 | 9.5 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。