- 學位論文
利用超臨界流體分散溶液法進行得舒緩與胭脂紅酸的微粒化與多晶型轉變
Micronization and Polymorphic transition of Erlotinib HCl and Carminic Acid from SEDS Technique
若您是本文的作者，可授權文章由華藝線上圖書館中協助推廣。
摘要
本研究以超臨界流體分散溶液(SEDS)法，針對原料藥得舒緩(Erlotinib HCl)與天然色素胭脂紅酸(Carminic acid)進行處理。主要目的為將原料藥與色素進行微粒化與多晶型轉變，以提升在人體中的溶離速率。 本研究首先以Erlotinib HCl進行參數效應之探討，探討在不同的溶劑、壓力、溫度及溶液流速下對粒徑大小與分布及多晶型之影響。研究結果顯示，在溶劑為甲醇、壓力為100bar、溫度為35℃、溶液濃度為100%飽和濃度、溶液流速為0.75 mL/min的情況下，可以得到Erlotinib HCl平均粒徑為0.98微米的顆粒，且多晶型由原始的Form B轉變為Form E，在人體胃液中之溶離速率，較原始藥物提升了2.68倍；當溶液流率提升為1 mL/min的情況下，可以得到Erlotinib HCl平均粒徑約0.99微米的顆粒，且多晶型由原始的Form B轉變為Form A，溶離速率較原始藥物提升了3.64倍。 本研究再以Carminic acid進行參數效應之探討，研究在不同的壓力、溫度、溶液濃度與溶液流速下對粒徑大小與分布及多晶型之影響。研究結果顯示，在溶劑為乙醇、壓力為100bar、溫度為35℃、溶液濃度為100%飽和濃度、溶液流率為1 mL/min的情況下，可得到Carminic acid平均粒徑約為0.15微米的顆粒，多晶型由原始的Form I轉為Form II，在人體胃液中之溶離速率，較原始色素提升了2.06倍；當溫度提升為為45℃，可得到Carminic acid平均粒徑約為0.18微米，多晶型由原始的Form I轉為Form III，溶離速率較原始色素提升了4.07倍。當溶液流率降為0.5 mL/min，可得到Carminic acid平均粒徑約為0.19微米的顆粒，多晶型為原始的Form I，溶離速率較原始色素提升了9.63倍。
並列摘要
The objective of this study was to investigate the application of solution enhanced by supercritical fluids (SEDS) technique for the micronization and polymorphic transition of Erlotinib HCl and Carminic acid. Using various operating parameters in SEDS result in different particle size and polymorphs. These parameters such as solvent, pressure, temperature, solution concentration, solution flow rate were investigated in order to find the optimum operating condition for increasing the dissolution rate in human body. For Erlotinib HCl, the results showed the mean particle size decreased from the original 20.74 μm to 0.98 μm, and the polymorphs changed from the original Form B to Form E under the following operating conditions：solvent=methanol, P=100bar, T=35℃, solution concentration=100% sat., solution flow rate=0.75 mL/min. The dissolution rate of this experimental result increased by 2.68 times to original Erlotinib HCl. Upon increasing the solution flow rate to 1 ml/min, the mean particle size decreased to 0.99 μm. The polymorphs changed to Form A, and the dissolution rate increased by 3.64 times. For Carminic acid, the mean particle size decreased from the original 18.39 μm to 0.15 μm, and the polymorphs changed from the original Form I to Form II under the following operating conditions：solvent=ethanol, P=100bar, T=35℃, solution concentration=100%sat., solution flow rate=1 mL/min. The dissolution rate of this experimental result increased by 2.06 times to original Carminic acid. Upon increasing temperature to 45℃, polymorphs changed to Form III and the dissolution rate increased by 4.07 times. Upon decreasing solution flow rate to 0.5 mL/min, polymorphs didn’t change and the dissolution rate increased by 9.63 times.
參考文獻
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, 國立台灣大學化學
Abd El-Aty A.M., Choi J.-H., Ko M.-W., Khay S., A. Goudah A., Shin H.-C., Kim J.-S., Chang B.-J., Lee C.-H., Shim J.-H., Approaches for application of sub and supercritical fluid extraction for quantification of orbifloxacin from plasma and milk: Application to disposition kinetics, Anal. Chim. Acta. 631 (2009) 108–115.
ACGIH, American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2001
Cao L-Q., Chen L.-P., Cui P.-Y., Wang J.-D., Synthesis of PNIPA/PDMS-g-PAA core-shell composites in supercritical carbon dioxide, J. Appl. Polym. Sci. 108 (2008) 3843-3850.
Chen C.-C, Wagner G., Vitamin E nanoparticle for beverage applications, Chem. Eng. Res. Des. 82 (2004) 1432–1437.