Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong, China.
School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, China.
Int J Pharm. 2019 Apr 5;560:35-46. doi: 10.1016/j.ijpharm.2019.01.025. Epub 2019 Jan 19.
The evaluation of particle size recommended in the pharmacopeias requires a constant flow rate, and the method for pediatric inhaled drugs is the same as for adult drugs. In this study, the aerosol concentration and particle size distribution (PSD) were measured under a realistic breathing pattern and constant flow. Two types of nebulizer (i.e., breath-enhanced nebulizer and vibrating-mesh nebulizer) and two formulations (i.e., budesonide suspension and albuterol solution) were chosen for comparison. The aerosol concentration under the realistic pattern was not constant, which was different from the result at constant flow. The changing trend of aerosol concentration varied with the operation process of each device. The aerosol concentration profile was similar between budesonide suspension and albuterol solution. As to the PSD, as inspiratory flow increased, the X50 (50% undersize) increased with all nebulizers but Omron microAir NE-U22 nebulizer. There was good agreement between X50 obtained under the realistic inhalation patterns and their equivalent average flow rates by Bland-Altman analysis, although the X50 obtained under the realistic inhalation pattern was greater than value at constant flow. The agreement of the two breath-enhanced jet nebulizers was better than that of the vibrating-mesh nebulizers. The X50 of budesonide was not equal to that of albuterol when using the same nebulizer. Interestingly, a significant difference was observed in the X50 and Span when comparing the results of PSD under adult and child breathing patterns. Furthermore, all vibrating-mesh nebulizers produced aerosol droplets having larger mean diameter and narrower size distribution than those of the air-jet nebulizers. We conclude that it will be more conducive to the evaluation of particle size to use a laser diffractometer under a realistic pattern and make up for the shortcomings of cascade impactors. The effects of flow pattern, nebulizer and formulation should be taken into account in the evaluation of the qualities of nebulizer products in pharmaceutical practice.
药典中推荐的粒径评估需要恒定的流速，儿科吸入药物的方法与成人药物相同。在这项研究中，在现实呼吸模式和恒流下测量了气溶胶浓度和粒径分布（PSD）。选择了两种雾化器（即呼吸增强型雾化器和振动网孔雾化器）和两种制剂（即布地奈德混悬液和沙丁胺醇溶液）进行比较。现实模式下的气溶胶浓度不是恒定的，这与恒流下的结果不同。气溶胶浓度的变化趋势随每个设备的操作过程而变化。布地奈德混悬液和沙丁胺醇溶液的气溶胶浓度分布相似。至于 PSD，随着吸气流量的增加，所有雾化器的 X50（50%下筛）都增加，但欧姆龙 microAir NE-U22 雾化器除外。通过 Bland-Altman 分析，现实吸入模式下获得的 X50 与其等效平均流速之间具有良好的一致性，尽管现实吸入模式下获得的 X50 大于恒流下的值。两种呼吸增强型射流雾化器的一致性优于振动网孔雾化器。使用相同的雾化器时，布地奈德的 X50 不等于沙丁胺醇的 X50。有趣的是，当比较成人和儿童呼吸模式下 PSD 的结果时，X50 和 Span 存在显著差异。此外，所有振动网孔雾化器产生的气溶胶液滴的平均直径大于空气射流雾化器，且粒径分布更窄。我们得出的结论是，在现实模式下使用激光衍射仪将更有利于粒径评估，可以弥补级联冲击器的不足。在药物实践中，应考虑流量模式、雾化器和制剂对雾化器产品质量的评估的影响。
