Micronization and Polymorphic transition of Erlotinib HCl and Carminic Acid from SEDS Technique

• Main Authors: Yao-Chun Tien, 田耀鈞
• Other Authors: Yan-Ping Chen
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/17139416846450712172

碩士 === 國立臺灣大學 === 化學工程學研究所 === 97 === 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.