Computational Fluid Dynamics (CFD) Guided Spray Drying Recommendations for Improved Aerosol Performance of a Small-Particle Antibiotic Formulation.
Computational Fluid Dynamics (CFD) Guided Spray Drying Recommendations for Improved Aerosol Performance of a Small-Particle Antibiotic Formulation.
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DOI：
10.1007/s11095-022-03180-7
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发表时间：
2022-03
影响因子：
3.7
通讯作者：
Hindle M
中科院分区：
文献类型：
--
作者：
Longest W;Hassan A;Farkas D;Hindle M
本研究的目的是实施计算流体动力学（CFD）模拟和气溶胶表征实验，以确定用于儿科空气喷射干粉吸入器（DPI）的妥布霉素赋形剂增强生长（Tobi-EEG）制剂的最佳喷雾干燥条件。实施了一种迭代方法，其中使用CFD模拟探索喷雾干燥条件组，然后进行候选先导物选择、粉末生产和体外气溶胶测试。进行小颗粒喷雾干燥器的CFD模拟以捕获在粉末收集区域中的液滴干燥参数和表面平均温度和相对湿度（RH）条件。使用儿科喷气DPI、级联冲击和通过儿科口-喉（MT）模型至气管过滤器的气溶胶输送，对选定粉末进行体外气溶胶试验。基于CFD模拟和体外粉末性能的比较，静电收集的小颗粒粉末的推荐干燥条件包括：（i）将CFD预测的干燥参数κavg和κmax分别降低到3 µm2/ms和114 µm2/ms以下;（ii）将收集器表面RH保持在升高的范围内，对于具有l-亮氨酸的Tobi-EEG制剂，其为20- 30%RH;以及（iii）基于溶质CFD参数的质量分数，确保到达收集器的颗粒被完全干燥。基于新推荐的用于小颗粒气溶胶的喷雾干燥器条件，先导Tobi-EEG制剂的递送性能得到改善，导致>60%的DPI负载剂量通过儿科MT模型。
The objective of this study was to implement computational fluid dynamics (CFD) simulations and aerosol characterization experiments to determine best-case spray drying conditions of a tobramycin excipient enhanced growth (Tobi-EEG) formulation for use in a pediatric air-jet dry powder inhaler (DPI). An iterative approach was implemented in which sets of spray drying conditions were explored using CFD simulations followed by lead candidate selection, powder production and in vitro aerosol testing. CFD simulations of a small-particle spray dryer were performed to capture droplet drying parameters and surface-averaged temperature and relative humidity (RH) conditions in the powder collection region. In vitro aerosol testing was performed for the selected powders using the pediatric air-jet DPI, cascade impaction, and aerosol transport through a pediatric mouth-throat (MT) model to a tracheal filter. Based on comparisons of CFD simulations and in vitro powder performance, recommended drying conditions for small-particle powders with electrostatic collection include: (i) reducing the CFD-predicted drying parameters of κavg and κmax to values below 3 µm2/ms and 114 µm2/ms, respectively; (ii) maintaining the Collector Surface RH within an elevated range, which for the Tobi-EEG formulation with l-leucine was 20–30 % RH; and (iii) ensuring that particles reaching the collector were fully dried, based on a mass fraction of solute CFD parameter. Based on the newly recommended spray dryer conditions for small particle aerosols, delivery performance of the lead Tobi-EEG formulation was improved resulting in >60% of the DPI loaded dose passing through the pediatric MT model.
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DOI：
10.1089/jamp.2019.1540
发表时间：
2019-08-29
影响因子：
3.4
作者：
Farkas, Dale;Hindle, Michael;Longest, Worth
通讯作者：
Longest, Worth
影响因子：
4.9
作者：
Baldelli, Alberto;Boraey, Mohammed A.;Vehring, Reinhard
通讯作者：
Vehring, Reinhard
影响因子：
5.8
作者：
Li, Liang;Leung, Sharon Shui Yee;Chan, Hak-Kim
通讯作者：
Chan, Hak-Kim
影响因子：
4.5
作者：
Bass K;Longest PW
通讯作者：
Longest PW
影响因子：
3.7
作者：
Farkas D;Bonasera S;Bass K;Hindle M;Longest PW
通讯作者：
Longest PW