以粒径为主要评价指标,采用单因素试验和正交设计,优化了超临界CO_2抗溶剂法制备微粉化阿西美辛的工艺条件。所得优化参数为:溶剂为丙酮∶二氯甲烷(1∶1),结晶压力16 MPa,结晶温度40℃,阿西美辛浓度9 mg/ml。优化得到的微粉化阿西美辛粒径降至6.02mm;扫描电镜、红外、差示量热扫描等分析结果表明,微粉化阿西美辛的理化性质与原料药相比没有发生明显变化。并且,微粉化阿西美辛在水中10 min的溶出率超过20%,80 min时接近80%,溶出性能相较于原料药得到明显改善。 Using particle size as the main evaluation index, single factor experiments and orthogonal design were used to optimize the process conditions for the preparation of micronized acemetacin by supercritical CO_2 anti-solvent method. The optimized parameters were as follows: the solvent was acetone: dichloromethane (1: 1), the crystallization pressure was 16 MPa, the crystallization temperature was 40 ℃ and the concentration of acemetac was 9 mg / ml. The results showed that the particle size of micronized acemetacin decreased to 6.02mm. The results of scanning electron microscopy, infrared and differential scanning calorimetry showed that the physicochemical properties of micronized acemetacin did not change significantly compared with that of drug substance. Moreover, the dissolution rate of micronized acemetacin in water exceeded 20% in water for 10 min and was close to 80% at 80 min, and the dissolution performance was significantly improved compared with the drug substance.