反溶剂重结晶法制备青蒿素超细粉体

采用反溶剂重结晶法进行了青蒿素超细粉体的制备研究。以乙醇为溶剂，水为反溶剂，系统考察了药用辅料类型、反溶剂溶剂体积比、药物溶液浓度和混合强度对产品颗粒形貌和大小的影响。结果表明，辅料羟丙甲纤维素(HPMC)与聚乙烯吡咯烷酮 (PVP)联用可有效控制颗粒形貌，反溶剂溶剂体积比为20，青蒿素乙醇溶液浓度为20 mg·ml^-1，搅拌转速为8000 r·min^-1时，浆料中可得到平均短径0.84 μm、长径3 μm的针状颗粒，此浆料经喷雾干燥可得到粒径为2～3 μm的类球形粉体颗粒。进一步采用红外光谱、X射线衍射、差热分析、比表面积测试对原料药及产品的特性进行了表征，结果显示，青蒿素经反溶剂重结晶过程与辅料HPMC间产生一定的氢键作用，超细粉体产品的结晶度及熔点降低，比表面积增至原料药的26.4倍。体外溶出测试结果表明，青蒿素超细粉体的溶出速率远优于原料药，超细药物粉体15 min即可溶出88.3%，而同期原料药的溶出度仅为2.1%。

Preparation of ultra-fine artemisinin by antisolvent recrystallization

Ultra-fine artemisinin(ART)was prepared by antisolvent recrystallization.Ethanol was used to form the artemisinin solution,and water was chosen as the antisolvent to induce precipitation.The effects of type of excipients,volume ratio of antisolvent to solvent,ART solution concentration and stirring speed on particle morphology and size were investigated.The results indicated that the combined use of hydroxypropyl methyl cellulose(HPMC)and polyviny pyrrolidone(PVP)as excipients could easily control the particle morphology.The needle-like ART particles with average width of 0.84 μm and average length of 3 μm were obtained under the following conditions:volume ratio of water to ethanol of 20,ART solution concentration of 20 mg·ml-1,stirring speed of 8000 r·min-1.The spray dried particles had spherical shape with 2—3 μm in diameter.The as-prepared ultra-fine ART product and raw ART were further characterized by Fourier transform infrared(FTIR)spectroscopy,X-ray diffraction(XRD),differential scanning calorimetry(DSC)and specific surface area test.The results indicated that hydrogen bonding was formed between ART and HPMC after recrystallization.Ultra-fine ART had a lower degree of crystallinity and a lower melting point than raw ART and its specific surface area was 26.4 times as high as that of raw ART.In dissolution tests,ultra-fine ART powder exhibited enhanced dissolution property compared to raw ART.88.3% of the ultra-fine ART powder was dissolved within 15 min.However,only 2.1% of raw ART was dissolved during the same period.