Micronization of dihydroartemisinin by rapid expansion of supercritical solutions

作者：Chingunpitak Jira****; Puttipipatkhachorn Satit^*; Tozuka Yuichi; Moribe Kunikazu; Yamamoto Keiji

来源：Drug Development and Industrial Pharmacy, 2008, 34(6): 609-617.

DOI：10.1080/03639040701833682

• micronization
• dihydroartemisinin
• supercritical fluid
• rapid expansion of supercritical solutions
• RESS

The purpose of this study was to prepare fine particles of antimalarial drug dihydroartemisinin (DHA) by rapid expansion of supercritical solutions (RESS) using carbon dioxide as supercritical fluid. The mechanical grinding by jet mill and additional vibration rod mill also was performed as a comparative method. In the RESS process, drug particles were prepared by varying processing conditions, including extraction condition, pre-expansion condition, nozzle diameter, nozzle temperature, and collecting distance. Particle size and morphology and physicochemical characteristics of the drug particles were investigated. The RESS process could produce the smaller drug particles (about 1-2 mu m) when compared to mechanical grinding method (about 7 mu m). All RESS processing parameters had an effect on size and morphology of drug particles. The particle size of drug was related to the solubility of drug in supercritical CO2 at each processing condition. The fine particles of DHA (about 1 mu m) with narrow size distribution could be obtained at extraction pressure of 18 MPa and extraction temperature of 32 degrees C, which was closed to the critical temperature of supercritical CO2 whereas broad size distribution was obtained at extraction temperature of 60 degrees C. Powder X-ray diffraction study indicated that the RESS-processed particles were in crystalline form. The results revealed that RESS process is applicable for micronization of DHA.

• 出版日期2008