Comparative Hygroscopic Aerodynamic Particle Sizing Measurements of the Hygroscopic Growth of Inhaled Pharmaceutical Ingredients

The size distribution of an inhaled pharmaceutical aerosol generated by a nebulizer is a critical parameter influencing the deposition and therapeutic effect of the medication. Relative humidity (RH) can alter size distribution by promoting particle growth through condensation, depending on the hygroscopicity of the formulation. In this study, we evaluate the effect of RH on mannitol, trehalose, salbutamol, and tobramycin aerosols using the Comparative Hygroscopic Aerodynamic Particle Sizing (CHAPS) technique under varying RH conditions, ranging from ambient to physiological levels. The results demonstrate that the RH significantly influences aerosol particle size, with particle growth becoming more pronounced as RH exceeds 95%. The findings confirm that understanding the relationship between geometric radial growth factors (rGF) from single droplet size measurements and the aerodynamic rGF is essential for more accurate prediction of plume size distribution, especially at lower RH levels. We also demonstrate consistency between the size distributions measured by CHAPS and a Next Generation Impactor (NGI), with CHAPS providing higher-resolution in size and time and data on actuation-by-actuation variability in size distribution and aerosol dose.

雾化器产生的吸入式药物气溶胶的粒径分布，是影响药物沉积行为与治疗效果的关键参数。相对湿度（Relative Humidity，RH）可通过冷凝作用促进颗粒生长，进而改变气溶胶粒径分布，其影响程度取决于制剂的吸湿性。本研究采用对比吸湿气动粒径分析（Comparative Hygroscopic Aerodynamic Particle Sizing，CHAPS）技术，在环境至生理水平的不同相对湿度条件下，评估了相对湿度对甘露醇、海藻糖、沙丁胺醇及妥布霉素气溶胶的影响。
研究结果表明，相对湿度对气溶胶颗粒粒径具有显著影响：当相对湿度超过95%时，颗粒生长现象会愈发显著。本研究证实，为更精准地预测气溶胶羽流的粒径分布（尤其是在较低相对湿度条件下），明确单液滴粒径测量所得的几何径向生长因子（rGF）与气动径向生长因子之间的关联至关重要。此外，本研究还验证了CHAPS与新一代撞击器（Next Generation Impactor，NGI）测得的粒径分布结果具有一致性；CHAPS可在粒径与时间维度上提供更高分辨率的数据，同时能够获取逐驱动的粒径分布变异性与气溶胶剂量信息。