Evaluation of Bio-relevant Mouth-Throat Models for Characterization of Metered Dose Inhalers
Evaluation of Bio-relevant Mouth-Throat Models for Characterization of Metered Dose Inhalers
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DOI：
10.1208/s12249-019-1339-6
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发表时间：
2019-04-01
影响因子：
3.3
通讯作者：
Guo, Changning
中科院分区：
文献类型：
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作者：
Kaviratna, Anubhav;Tian, Geng;Guo, Changning
对于吸入药物表征，传统上使用的USP诱导端口提供有限的体内预测能力，因为它不能充分模拟气道几何形状。在这项研究中，使用两种定量吸入器（MDI）药物产品评估了各种生物相关的口-喉（MT）模型，包括阿尔伯塔理想化喉（AIT）和3D打印的大/中/小尺寸VCU（弗吉尼亚联邦大学）模型：含有丙酸倍氯米松的溶液MDI（BDP-MDI）和含有丙酸氟替卡松的混悬液MDI（FP-MDI）。对于BDP-MDI，与其他MT模型相比，使用VCU大MT和小MT模型导致显著更高的MT沉积和更低的细颗粒分数（FPF）。在FP-MDI的情况下，与USP诱导端口和AIT相比，三种VCU模型导致更高的MT沉积和更低的FPF。总体而言，与溶液MDI相比，混悬MDI的体外试验结果对MT模型的几何差异更敏感。我们的研究结果表明，MDI产品的体外表征可能受到许多因素的影响，包括配方类型，MT几何形状，形状，内部空间体积和用于制作MT模型的材料。
For inhalation drug characterization, the traditionally used USP induction port provides limited in vivo predictive capability because it does not adequately mimic airway geometry. In this study, various bio-relevant mouth-throat (MT) models, including Alberta Idealized Throat (AIT), and 3D printed large/medium/small-sized VCU (Virginia Commonwealth University) models were evaluated using two metered dose inhaler (MDI) drug products: a solution MDI containing beclomethasone dipropionate (BDP-MDI) and a suspension MDI containing fluticasone propionate (FP-MDI). For BDP-MDI, use of VCU large and small MT models resulted in a significantly higher MT deposition and lower fine particle fraction (FPF) compared with the other MT models. In the case of FP-MDI, the three VCU models resulted in higher MT deposition and lower FPF compared with the USP induction port and AIT. Overall, the in vitro testing results for the suspension MDI were more sensitive to geometric differences of the MT models than those for the solution MDI. Our results suggest that in vitro characterization of MDI products can be influenced by many factors, including the type of formulation, the MT geometry, shape, internal space volume, and the material used to make the MT models.