目的选用BüCHI超声波控制器为主要设备,以疏水性药物HNN为模型药物进行超声波喷雾干燥改善药物的制剂特性,从粉体学性质、晶型以及化学稳定性3个方面比较超声喷雾干燥前后药物的主要性质变化。方法测定药物粒径分布、密度、休止角等主要的粉体学性质,并以扫描电镜考察其微观形态;采用DSC、IR、XRPD、Raman分析技术对药物晶型进行表征;采用HPLC按照自身对照法计算药物有关物质含量。结果原料药粒径分布在4.44~1 710μm,分布宽且不均匀,喷雾干燥后粒径分布在50~300μm间,分布更窄,更均匀,且呈现正态分布;堆密度由0.054 5 g·cm~(-3)增加到0.515 4 g·cm~(-3),提高到原料药的9.5倍;休止角由57.26°降至37.21°,已经接近粉末直接压片的要求;扫描电镜原料药的微观形态为针状,杂乱无章,而喷雾干燥后为球状圆整颗粒,粒径均一;DSC结果显示喷雾干燥前后熔点没有改变,IR、XRPD、Raman结果表明药物特征峰前后一致,药物晶型无变化;有关物质化学稳定试验结果表明喷雾干燥工艺对药物稳定性没有影响。结论超声波喷雾干燥的颗粒圆整均一,极大地优化了HNN药物的制剂特性,这种依靠超声波能量雾化的低剪切方式,最大程度的保护了药物的晶型及稳定性,可以作为类似药物处方前研究的一个可选方式进行药物制剂相关特性的优化。 Objective To select the BüCHI ultrasonic controller as the main equipment and to use the hydrophobic drug HNN as the model drug to improve the preparation properties of the drug by ultrasonic spray drying. The properties of the drug before and after ultrasonic spray drying were compared among three aspects: powder science, crystal form and chemical stability The main changes in nature. Methods The main powder properties such as drug particle size distribution, density and angle of repose were determined. The microscopic morphology was observed by scanning electron microscopy. The crystalline forms of the drug were characterized by DSC, IR, XRPD and Raman analysis. Act to calculate the drug-related substance content. Results The particle size distribution of the drug substance ranged from 4.44 to 1 710 μm and its distribution was wide and inhomogeneous. The particle size distribution of spray-dried granules varied from 50 μm to 300 μm. The particle size distribution was narrower and more uniform with a normal distribution. The bulk density ranged from 0.054 5 g · cm -3 increased to 0.515 4 g · cm -3 and increased to 9.5 times that of bulk drug. The angle of repose decreased from 57.26 ° to 37.21 °, which was close to that of powder direct tabletting. SEM, The results showed that the melting point did not change before and after spray drying. The results of IR, XRPD and Raman showed that the characteristic peaks of the drug were consistent before and after, and the crystal form of the drug did not change Changes; the chemical stability test results show that the spray drying process has no effect on drug stability. Conclusion Ultrasound spray-dried particles are uniform and round, which greatly optimizes the preparation characteristics of HNN drugs. The low-shear mode relies on ultrasonic energy atomization to maximally protect the crystal form and stability of the drug and can be used as a similar drug An alternative to pre-prescription studies is the optimization of drug formulation-related properties.