跳到主要內容

臺灣博碩士論文加值系統

(3.236.84.188) 您好!臺灣時間:2021/08/01 19:58
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:塗淑玲
研究生(外文):Shu-Ling Tu
論文名稱:以液-液注射方式成型均一尺寸微粒及其固化機制之研究
論文名稱(外文):A study on the solidification mechanism of uniform size microspheres prepared by liquid-liquid injection method
指導教授:蔡瑞瑩
指導教授(外文):Ruey-Yug Tsay
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫學工程研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:65
中文關鍵詞:液-液注射方式微粒形態相分離
外文關鍵詞:Liquid-liquid injection methodMicrospheresMorphologyPhase separation
相關次數:
  • 被引用被引用:0
  • 點閱點閱:139
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
藥物之釋放特性與微粒之大小及其內部之孔洞結構,有非常直接之關係。文獻上,諸多製備方式多無法對微粒尺寸及孔隙度作精準之控制,同時微粒沾黏的問題也急需改善。本研究以液-液注射方式在高注射流速下,探討製備均一尺寸微粒之效果,並藉由相分離機制,探討微粒固化對微粒孔洞性之影響。結果顯示當流速大於液柱產生臨界值,進入液柱成型階段後,液滴尺寸將趨近於定值,而受流速影響小,在此階段操作,可製得尺寸十分均勻之微粒。本研究即操作在此流速範圍製備均勻微粒藉以探討固化機制。固化試驗結果顯示微粒內部之孔洞,為非溶劑(nonsolvent)滲入微粒中,造成液-液相分離所形成,隨著以水相萃取時間之增加,孔洞往中心移動。濃度及微粒尺寸於長時間下影響微粒內孔洞形成之機制效果十分顯著。非溶劑累積於濃度1/50之微粒表層,導致相分離之速率較快,而使表層之孔洞數目增加,堆疊為孔隙度高之海綿狀。然而高濃度之高分子溶液,因黏度高,故而減緩非溶劑滲入之速率,導致相分離機制係以高分子貧相成核成長之方式進行。本研究亦探討退火處理方式對微粒固化機制之影響,結果顯示退火處理可有效降低孔隙度。定性分析結果得知微粒之製備對高分子之玻璃轉移溫度及其分子量影響並不顯著,故可維持高分子之力學性質。
The size of microspheres and its inner pore structure have a direct influence on the character of drug release. However, microspheres prepared by traditional technologies generally have the problems of nonuniformilty on the size and pores structure. In the mean time, the aggregation between microspheres is also a problem needed to be resolved. This study investigated the performace of preparing uniform microspheres at high injection rate by a liquid-liquid injection method and the effects of solidification on the pore structure of microspheres by phase separation mechanism. The results indicated that the size of the microspheres approaches a constant value as the injection velocity reaches a critical value and enters the jet formation stage. In this study, uniform sized microspheres were prepared in this jet formation region. Our study indicates the pores in microspheres were formed by liquid-liquid phase separation induced by nonsolvent infiltration. The porous zone propagated inward with the increase of solidification time. Besides, the effects of polymer concentration and the size of microspheres were remarkable for prolonged solidification. For DLPLA concentration of 1/50, the accumulation of nonslovent at the surface of microspheres causes the faster phase separation and results in an increase in the number of pore, which eventually piles up and forms a spongy subsurface layer. While, for a higher polymer concentration, due to its high viscosity, the infiltration rate of nonsolvent is reduced and the phase separation occurs by the mechanism of nucleation-and-growth of polymer-poor phase. The effects of annealing were also studied. It indicated that pores within microspheres could be reduced effectively by annealing treatment. Microspheres characterization revealed that the preparation process had minor effect on molecular weight and glass transition temperature of the polymer. Therefore the polymer can maintain its mechanical properties.
1.Brian, A. Pharmaceutical Research, 16, 1140-1143, 1999.
2.Cannizzaro, S.M. and Langer, R.S., Chemical Review, 99, 3181-3198, 1999.
3.Storm, G., Belliot, S.O., Daemen and Lasic, D.D., Advanced Drug Delivery Reviews, 17, 31-48, 1995.
4.Uhrich, K.E., Cannizzaro, S.M., Langer, R.S. and Shakesheff, K.M., Chemical Review, 99, 3181-3198, 1999
5.Wu,X.S., (1995). Preparation, characterization, and drug delivery application of microspheres based on biodegradable lactic/glycolic acid polymers. In Wise, D.L. et al (Ed.), Encyclopedic handbook of biomaterials and bioengineering(pp.1015-1052). New York: Marcel Dekker.
6.Middleton, J.C., Tipton, A.J., Biomaterials, 21, 2335-2346, 2000.
7.Jain, R. A., Biomaterials, 21, 2475-2490, 2000.
8.Hausberger, A.G. and DeLuca, P.P., Journal of Pharmaceutical and Biomedical Analysis, 13, 747-760, 1995
9.Mehta, R.C., Jeyanthi, R., Calis, S., Thanoo, B.C., Burton, K.W., and DeLuca, P.P., Journal of Controlled Release, 29, 375-384, 1994.
10.Anderson, J.M. and Shive, M.S., Advanced Drug Delivery Reviews, 28, 5-24, 1997.
11.Grizzi, I., Garreau, H., Li, S. and Vert, M., Biomaterials, 16, 305-311, 1995.
12.Sansdrap, P. and Moës, A.J., Journal of Controlled Release, 43, 47-58, 1997.
13.Dunne, M. O.I. Corrigan and Ramtoola, Z., Biomaterials, 21, 1659-1668, 2000.
14.Prior, S., Gamazo, C., Irache, J.M., Merkle, H.P. and Gander, B., International Journal of Pharmaceutics, 196, 115-125, 2000.
15.Fu, K., Pack, D.W., Klibanov, A.M. and Langer, R., Pharmaceutical Research, 17, 100-106, 2000.
16.Prior, S., Gamazo, C., Irache, J.M., Merkle, H.P. and Gander, B., International Journal of Pharmaceutics, 196, 115-125, 2000.
17.Fu, Y.J., Shyu, S.S., Su, F.H. and Yu, P.C., Colloids and Surface B: Biounterface, 25, 269-279, 2002.
18.Berkland, C., King, M., Cox, A.,Kim, K. and Pack, D.W., Journal of Controlled release, 82,137-147, 2002.
19.Berkland, C., Kim, K. and Pack, D.W., Journal of Controlled release, 73,59-74, 2001.
20.Gliftm, R. (1978). Formation and breakup of fluid particles. In Grace, J.R. and Weber, M.E. (Ed.), Bubble, Drop, and Particles(pp. 321-351). New York: Academic Press.
21.劉育秉 均勻尺寸微粒成型機構研究 國立陽明大學醫學工程研究所 2003
22.Dabora, E.K., The Review of Scientific Instruments, 38, 502-506, 1966.
23.Marshall, W.R., (1954). Principles of jet breakup. Atomization and spray drying(pp 3-11). New York: American Institude of Chemical Engineers.
24.Lefebvre, A.H., (1989). Basic processes in atomization. In Chiger, N., (Ed.), Atomization and sprays(pp 27-78), New York: Hemisphere Publishing Corporation.
25.Edlund, U. and Albertsson, A.C., Journal of Polymer Science: Part A: Polymer Chemistrys, 38, 786-796, 2000.
26.Yang, Y.Y., Chia, H.H. and Chung, T.S., Journal of Controlled Release, 69, 81-96, 2000.
27.Yang, Y.Y., Chung, T.S., Bai, X.L. and Chan, W.K., Chemical Engineering Science, 55, 2223-2236, 2000
28.Li, W.I., Andersin, K.W., Mehta, R.C. and DeLuca, P.P., Journal of Controlled Release, 37, 199-214, 1995.
29.Van de Witte, P., Dijkstra, P.J., Van den Berg, J.W.A. and Feijen, J., Journal of Membrane Science, 117 ,1-31, 1996.
30.Van de Witte, P., Dijkstra, P.J., van den Berg, J.W.A. and Feijen, J., Journal of Polymer Science: Part B: Polymer Physics, 34, 2553-2568, 1996
31.Van de Witte, P., Dijkstra, P.J., van den Berg, J.W.A. and Feijen, J., Journal of Polymer Science: Part B: Polymer Physics, 35, 763-770, 1997.
32.Van de Witte, P., Esselbrugge, H., Dijkstra, P.J., van den Berg, J.W.A. and Feijen, J., Journal of Membrane Science, 113, 223-236, 1996.
33.Van de Witte, P., Esselbrugge, H., Dijkstra, P.J., Van den Berg, J.W.A. and Feijen, J., Journal of Polymer Science: Part B: Polymer Physics, 34, 2569-2578, 1997.
34.MuHugh, A.J. and Tsay, C.S., Journal of Applied Polymer Sciences, 46, 2011-2021, 1992.
35.P.D. Graham, Brodbeck, K.J. and MuHugh, A.J., Journal of Controlled Release, 58, 233-245, 1999.
36.蕭展之 DL-PLA藥物包覆微粒成型及降解機制探討 國立陽明大學醫學工程研究所 2004
37.Ruff, K., Pilhofer, T. and Mersmann, A., Chem.-Ing.-Tech., 48, 759, 1976
38.Skelland, A.H.P. and Hung, Y.F., AIChE Journal, 25, 180, 1979
39.Sah, H., Journal of Controlled Release, 47, 233-245, 1997
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top