1 Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University , Richmond, Virginia.
2 Food and Drug Administration , Rockville, Maryland.
J Aerosol Med Pulm Drug Deliv. 2017 Oct;30(5):339-348. doi: 10.1089/jamp.2016.1349. Epub 2017 Mar 23.
The dose and aerodynamic particle size distribution (APSD) of drug aerosols' exiting models of the mouth and throat (MT) during a realistic inhalation profile (IP) may be estimated in vitro and designated Total Lung Dose, TLD, and APSD, respectively. These aerosol characteristics likely define the drug's regional distribution in the lung.
A general method was evaluated to enable the simultaneous determination of TLD and APSD for budesonide aerosols' exiting small, medium and large VCU-MT models. Following calibration of the modified next generation pharmaceutical impactor (NGI) at 140 L/min, variations in aerosol dose and size exiting MT were determined from Budelin Novolizer across the IPs reported by Newman et al., who assessed drug deposition from this inhaler by scintigraphy.
Values for TLD from the test inhaler determined by the general method were found to be statistically comparable to those using a filter capture method. Using new stage cutoffs determined by calibration of the modified NGI at 140 L/min, APSD profiles and mass median aerodynamic diameters at the MT exit (MMAD) were determined as functions of MT geometric size across Newman's IPs. The range of mean values (n ≥ 5) for TLD and MMAD for this inhaler extended from 6.2 to 103.0 μg (3.1%-51.5% of label claim) and from 1.7 to 3.6 μm, respectively.
The method enables reliable determination of TLD and APSD for aerosols likely to enter the trachea of test subjects in the clinic. By simulating realistic IPs and testing in different MT models, the effects of major variables on TLD and APSD may be studied using the general method described in this study.
在真实的吸入轮廓（IP）中，从口腔和喉咙（MT）中出来的药物气溶胶的剂量和空气动力学颗粒大小分布（APSD）可以在体外进行估计，并分别指定为总肺剂量（TLD）和 APSD。这些气溶胶特征可能定义了药物在肺部的区域分布。
评估了一种通用方法，以能够同时确定布地奈德气溶胶从小、中、大 VCU-MT 模型中出来的 TLD 和 APSD。在对 140L/min 下的改良下一代制药冲击器（NGI）进行校准后，根据纽曼等人报告的 IP，从 Budelin Novolizer 中确定 MT 中出来的气溶胶剂量和大小的变化，他们通过闪烁扫描评估了这种吸入器的药物沉积。
通过通用方法确定的测试吸入器的 TLD 值被发现与使用过滤器捕获方法的 TLD 值具有统计学可比性。使用在 140L/min 下校准的改良 NGI 确定的新阶段截止值，在纽曼的 IP 范围内，作为 MT 出口处的几何尺寸的函数，确定了 APSD 分布和质量中值空气动力学直径（MMAD）。该吸入器的 TLD 和 MMAD 的平均值（n≥5）范围分别为 6.2 至 103.0μg（标签声称的 3.1%至 51.5%）和 1.7 至 3.6μm。
该方法能够可靠地确定可能进入临床受试者气管的气溶胶的 TLD 和 APSD。通过模拟真实的 IP 并在不同的 MT 模型中进行测试，使用本研究中描述的通用方法可以研究主要变量对 TLD 和 APSD 的影响。
