Cinnarizine與Diuron於超臨界二氧化碳中固體溶解度與微粒化之研究

Investigation on solubility and micronization of cinnarizine and diuron in supercritical carbon dioxide

邱志龍(Jhih-Long Ciou)

指導教授 ： 蘇至善

國立臺北科技大學/工程學院/化學工程研究所/碩士(2014年)

https://doi.org/10.6841/NTUT.2014.00879

摘要

本研究進行固體溶質於超臨界二氧化碳中溶解度與微粒化之研究。使用半流動式設備量測桂利嗪(Cinnarizine)與敵草隆(Diuron)於超臨界二氧化碳中的固體溶解度。量測溫度為308.2 K、318.2 K與328.2 K，量測壓力範圍由10至20 MPa。在每一實驗溫度與壓力下，至少量測三次固體溶解度數據，重複量測的變異係數均小於6 %。經實驗量測出桂利嗪(Cinnarizine)與敵草隆(Diuron)的溶解度莫耳分率範圍皆為10-7~10-5。並使用兩無因次半經驗式以及無因次溶液模式來迴歸量測的固體溶解度數據，皆可得到合理之迴歸計算結果。此外，本研究亦使用超臨界溶液快速膨脹法將敵草隆(Diuron)進行微粒化。微粒化後的微粒使用掃描式電子顯微鏡、傅立葉轉換紅外線光譜儀、微分掃描式熱卡計與雷射散射粒徑分析儀進行物性分析。敵草隆(Diuron)的平均粒徑經過微粒化後，從原本的12.7微米縮小至6.1微米，且經處理前後，粉體之物性沒有改變。

關鍵字

固體溶解度 ； 超臨界溶液快速膨脹 ； 微粒化 ； 再結晶

並列摘要

In this study, measurement of solid solubility in supercritical carbon dioxide and micronization of solid solute using rapid expansion of supercritical solutions process (RESS) are studied. The solubilities of cinnarizine and diuron in supercritical carbon dioxide are measured using a semi-flow type apparatus. The experimental data are measured at three isotherms of 308.2 K, 318.2 K and 328.2 K, with pressure range from 10 to 20 MPa. At least three measurements are made for each reported solubility at a given temperature and pressure. The coefficient of variance of reported solubility is below 6 %. The solubilities of cinnarizine and diuron are in the mole fraction range of 10-7 to 10-5. The measured solubility data are then correlated by dimensionless Mendez–Santiago–Teja and dimensionless Chrastil model. In addition, a dimensionless solution model is also employed to fit the measured data. The deviations in the solid solubility correlation using three models are about 3-10 %. For RESS study, diuron is successfully micronized in this study. The micronized particles are analyzed by scanning electron microscope (SEM), Fourier transform infrared spectrometer (FTIR), differential scanning calorimeter (DSC) and laser light scattering particle size analyzer. The mean particle size of diuron is micronized from its original 12.7 to 6.1μm.

並列關鍵字

Solid solubility ； Rapid expansion of supercritical solutions ； Micronization ； Recrystallization

參考文獻

47.蘇至善，藥物固體於超臨界二氧化碳中溶解度與微粒化之研究，國立臺灣大學工學院化學工程學研究所博士論文 (2007)

1.Arai, K., Smith Jr., R. L. and Aida, T. M., Decentralized chemical processes with supercritical fluid technology for sustainable society, J. Supercrit. Fluids, 47 (2009) 628–636

2.Asiabi, H., Yamini, Y., Tayyebi, M., Moradi, M., Vatanara, A. and Keshmiri, K., Measurement and correlation of the solubility of two steroid drugs in supercritical carbon dioxide using semi empirical models, J. Supercrit. Fluids, 78 (2013) 28–33

3.Baseri, H. and Lotfollahi, M. N., Formation of gemfibrozil with narrow particle size distribution via rapid expansion of supercritical solution process (RESS), Powder Technol., 235 (2013) 677-684

4.Brunner, G., Supercritical fluids: technology and application to food processing, J. Food Eng., 67 (2005) 21–33