以批式氣體反溶劑沉積法進行藥物之微粒化研究

Micronization of Pharmaceutical Compounds Using Batch Gas Anti-Solvent Precipitation

游議輝(Yi-Huei Yu)

指導教授 ： 陳延平

國立臺灣大學/工學院/化學工程學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.02129

摘要

本研究將探討以氣體反溶劑沉積法(Gas Anti-Solvent Precipititation，GAS)進行藥物之微粒化，目標藥物包括carbamazepine、carisoprodol、gallic acid、nitrofurantoin、salicylsalicylic acid、sulindac及terfenadine等七種，使用的反溶劑為二氧化碳，先行測試微粒化之可行性，以SEM觀察微粒化之效果，得到最佳微粒化之藥物為sulindac。
其後以sulindac進行微粒化參數探討，分別針對溶劑種類、升壓速率、溶液濃度、溫度、末壓、溶液填量等操作變數，探討各變數對粒徑及晶型的影響。由SEM的結果可以發現經處理後，蘇林達克的粒徑有非常明顯的改變，形成不規則片狀的藥物顆粒。由XRD的分析可以發現蘇林達克之晶型受到操作變數的影響，而有明顯的改變，部分的操作變數僅會對結晶晶面造成影響，部分的操作變數則對藥物的結晶晶面與晶型有相當程度的影響。在DSC的結果中顯示並無固態之相轉移，而由SEM的結果也可看出顆粒外部並無明顯變化。

關鍵字

藥物微粒化 ； 氣體反溶劑法 ； 超臨界

並列摘要

Micronization of seven pharmaceutical compounds, carbamazepine, carisoprodol, gallic acid, nitrofurantoin, salicylsalicylic acid, sulindac and terfenadine by using batch gas antisolvent precipitation (GAS) was investigated in this research. SEM showed the micronization of particles

Sulindac was investigated for the effect of some key process parameters. Carbon dioxide was used as an antisolvent. Methanol, ethanol and acetone were used as solvents. Particle morphology was determined by SEM which showed the particles had irregular shapes after the GAS process. Crystal structure analyzed by XRD showed different crystal habits after the GAS process. Further investigation by DSC demonstrated no phase transition and decomposition on sulindac. Process parameters, such as solvent used, solution amount, pressurized type, final pressure, temperature and solution concentration were investigated. The micronized sulindac with sizes of 1μm was obtained from 3mL acetone solution which was 90% of saturation at 298K after rapid pressurized up to 120 bar.

並列關鍵字

GAS ； antisolvent ； supercritical ； micronization

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