中文摘要：

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。

英文摘要：

OBJECTIVE To improve the pharmaceutical attributes of the hydrophobic drug HNN as the model drug by the Ultrasonic spray-drying technique while BüCHI ultrasonic controller was using as the main equipment. The main properties of the drugs HNN, powder properties, crystal morphology and chemical stability were compared to evaluate the fuction of the ultrasonic spray drying. METHODS The main powder properties such as drug particle size distribution, density and angle of repose were measured, and the microstructure was investigated by scanning electron microscopy. Characterization spectrum of drugs were detected by DSC, IR, XRPD and Raman analysis. HPLC was used to determine the contents of the related substances of drugs. RESULTS The particle size of the drug substance was 4.44-1 710 μm, that of spray dried drug was 50-300 μm, the size distribution was narrower and more uniform, and showed a normal distribution. The bulk density of spray dried drug was increased by 9.5 times from 0.054 5 g·cm~（-3） to 0.515 4 g·cm~（-3）. Angle of repose was discreased from 57.26° to 37.21° that had been close to the requirements of direct compression of the powder. The microscopic morphology structure of the drug substance was needle-like, chaotic, but the spray-dried drug exhibits spherical round particles in the same size. The DSC showed no change in melting point. IR, XRPD and Raman showed consistent in drug characteristic peaks. These results told that there were no significantly different in the crystal types of drugs. The results of the relevant substances chemical stability test indicated that the spray drying process had any negative inflence on drug stability. CONCLUSION The spray-dried particles produced by ultrasonic nozzle are observed to be more rounded and uniform in terms of size and shape. Moreover, the pharmaceutical attributes of drug have been greatly optimized. The ultrasonic nozzle used in this study provide more protection on polymorphs and stability based on the low shear mode of ultrasonic energy