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標題: | 應用超臨界溶液快速膨脹法進行藥物Antipyrine、 Benzocaine與4-Dimethylaminoantipyrine之微粒化研究 Study of the RESS Process for Micronization of Antipyrine, Benzocaine and 4-Dimethylaminoantipyrine |
作者: | Chai-Siah Lee 李彩霞 |
指導教授: | 陳延平 |
關鍵字: | 微粒化,超臨界溶液快速膨脹法 (RESS),Antipyrine,Benzocaine,4-Dimethylaminoantipyrine,藥物多晶型,溶離速率, Micronization,RESS,Antipyrine,Benzocaine,4-Dimethylaminoantipyrine,Polymorphism,Dissolution, |
出版年 : | 2010 |
學位: | 碩士 |
摘要: | 本研究主要是利用超臨界溶液快速膨脹法 (RESS),針對藥物antipyrine、benzocaine與4-dimethylaminoantipyrine進行再結晶與微粒化研究。經由RESS程序,可將其藥物antipyrine之平均粒徑由原始的35.12 μm減小至2.28 μm,經由微粒化後,除了平均粒徑有明顯的變小外,其粒徑分佈也變得較窄。針對不同操作參數之探討,可觀察到萃取溫度、膨脹前溫度與膨脹後溫度,其對微粒化後之粒徑大小並無太大的影響。而經由微粒化過後之藥物,其溶離速率並沒有明顯的提效果。
對benzocaine而言,經由RESS程序,可將其平均粒徑由原始的153.33 μm減小至3 μm,經由微粒化後,除了平均粒徑有明顯的變小外,其粒徑分佈也變得較窄。針對不同操作參數之探討,可觀察到膨脹前溫度、膨脹後溫度與噴嘴內徑,其對微粒化後之粒徑大小並無太大的影響。而經由微粒化過後之藥物,其溶離速率有顯著的提升效果,可比原始藥物快2.44倍。 而原始藥物4-dimethylaminoantipyrine之平均粒徑分佈非常廣,約為22到2648 μm之間。而經由RESS程序後,其粒徑分佈則明顯的變得較窄,最小平均粒徑約為1.92 μm。同時亦探討不同操作參數此程序之影響,包含膨脹前溫度、膨脹後溫度與噴嘴內徑。可觀察到膨脹前溫度與膨脹後溫度,對於微粒化後之粒徑大小、分佈與結晶外觀有明顯的影響。且經由微粒化操作,其藥物可由原始的晶型Form I轉變成晶型Form II與Form III。同樣的,經由微粒化過後之藥物,其溶離速率亦有顯著的提升效果,可比原始藥物快4.37倍。 In this study, RESS process was applied for recrystallization and micronization of three model drugs including antipyrine, benzocaine and 4-dimethylaminoantipyrine. After RESS treatment, the physicochemical properties of the precipitated particles were evaluated by SEM, DSC, FTIR, and XRD analysis. In addition, the dissolution rate studies were conducted to investigate the influence of particle size reduction on the bioavailability of drug. For antipyrine, the particle size was significantly reduced from 35.12 μm to 2.28 μm using RESS method. The processed samples showed narrow size distribution. The variation of some process parameters including extraction temperature, pre-expansion temperature and post-expansion temperature had slight effect on the mean particle size. It was discovered that micronized antipyrine did not revealed noticeable enhancement on the dissolution profile. After RESS process, benzocaine particles were successfully micronized from original size of 153.33 μm to around 3 μm with much narrower size distribution. The effect of pre-expansion temperature, post-expansion temperature and nozzle diameter on the mean particle size and size distribution was studied; and slight influence was noticeable. Dissolution studies showed that dissolution rate of processed particles was enhanced by 2.44 times with new dissolution profile. The untreated 4-dimethylaminoantipyrine was large in size with very wide size distribution ranging from 22 μm to 2468 μm. With RESS treatment, the mean particle size of the drugs was drastically reduced to submicron size, in the range of 1.92 to 7.64 μm. Furthermore, very uniform and narrow size distribution was obtained after RESS micronization. Several operating parameters including pre-expansion temperature, post-expansion temperature and nozzle diameter were investigated. It was proved that pre-expansion temperature and post-expansion temperature have significant effect on the mean particle size, size distribution and morphology. In addition, DSC and XRD results showed that there was polymorphic transformation during RESS process. From dissolution rate study, the results demonstrated that higher dissolution efficiency (enhance degree = 4.37) was obtained as a consequence of significant particle size reduction. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46733 |
全文授權: | 有償授權 |
顯示於系所單位: | 化學工程學系 |
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