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In Vitro and In Silico Investigations on Drug Delivery in the Mouth-Throat Models with Handihaler®

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Abstract

This work aimed to evaluate the relative inhalation parameters that affect the deposition of inhaled aerosols, including mouth-throat morphology, airflow rate, and initial condition of emitted particles. In vitro experiments were conducted using the US Pharmacopeia (USP) throat and a realistic mouth-throat (RMT) with Handihaler®. Then, in silico study of the gas-solid flow was performed by computational fluid dynamics and discrete phase method. Results indicated that aerosol deposition in RMT was higher compared to that in USP throat at an airflow rate of 30 L/min, with 33.16 ± 7.84% and 21.11 ± 7.1% lung deposition in USP throat and RMT models, respectively, which showed a better correlation with in vivo data from the literature. Increasing airflow rate resulted in better drug aerosolization, while the fine particle dose trend ascended before declining, with the peak value obtained at a flow rate of 40 L/min. Overall, the effect of geometrical variation was more significant. Additionally, in silico results demonstrated clearly that the initial conditions of the emitted particles from inhalers affected the subsequent deposition. Larger momentum possessed by the central aerosol jet entering the mouth directly led to stronger impaction, which resulted in the deposition in the front region of mouth-throat models. This study is beneficial to develop an in silico method to understand the underlying mechanisms of in vivo mouth-throat deposition.

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Acknowledgments

Financial supports from Jiangsu Province for Distinguished Professorship Program and National (Zhenbo Tong), National Key R&D Project of China (2021YFB1715500), and Postgraduate Research&Practice Innovation Program of Jiangsu Province (No. KYCX17_0076) are sincerely acknowledged.

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Authors and Affiliations

  1. School of Energy and Environment, Southeast University, Nanjing, 210096, China

    Fen Huang, Wen Dai, Zhenbo Tong & Aibing Yu

  2. Department of Chemical Engineering, Monash University, Clayton, Vic, 3800, Australia

    Fen Huang, Xudong Zhou & Aibing Yu

  3. Institute for Process Modelling and Optimization, JITRI, Suzhou, 215000, China

    Jiaqi Yu

  4. Jiangxi Provincial Key Laboratory for Simulation and Modelling of Particulate Systems, Jiangxi University of Science and Technology, Nanchang, 330013, China

    Zongyan Zhou

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Huang, F., Zhou, X., Dai, W. et al. In Vitro and In Silico Investigations on Drug Delivery in the Mouth-Throat Models with Handihaler®. Pharm Res 39, 3005–3019 (2022). https://doi.org/10.1007/s11095-022-03386-9

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