Understanding the effects of inhaler resistance on particle deposition behaviour – A computational modelling study

Background and objective: Understanding the impact of inhaler resistance on particle transport and deposition in the human upper airway is essential for optimizing inhaler designs, thereby contributing to the enhancement of the therapeutic efficacy of inhaled drug delivery. This study demonstrates the potential effects of inhaler resistance on particle deposition characteristics in an anatomically realistic human oropharynx and the United States Pharmacopeia (USP) throat using computational fluid dynamics (CFD). Method: Magnetic resonance (MR) imaging was performed on a healthy volunteer biting on a small mockup inhaler mouthpiece. Three-dimensional geometry of the oropharynx and mouthpiece were reconstructed from the MR images. CFD simulations coupled with discrete phase modelling were conducted. Inhaled polydisperse particles under two different transient flow profiles with peak inspiratory flow rates (PIFR) of 30 L/min and 60 L/min were investigated. The effect of inhaler mouthpiece resistance was modelled as a porous medium by varying the initial resistance (Ri) and viscous resistance (Rv). Three resistance values, 0.02 kPa0.5minL−1, 0.035 kPa0.5minL−1 and 0.05 kPa0.5 minL−1, were simulated. The inhaler outlet velocity was set to be consistent across all models for both flow rate conditions to enable a meaningful comparison of models with different inhaler resistances. Result: The results from this study demonstrate that investigating the effect of inhaler resistance by solely relying on the USP throat model may yield misleading results. For the geometrically realistic oropharyngeal model, both the pressure and kinetic energy profiles at the mid-sagittal plane of the airway change dramatically when connected to a higher-resistance inhaler. In addition, the geometrically realistic oropharyngeal model appears to have a resistance threshold. When this threshold is surpassed, significant changes in flow dynamics become evident, which is not observed in the USP throat model. Furthermore, this study also reveals that the impact of inhaler resistance in a geometrically realistic throat model extends beyond the oral cavity and affects particle deposition downstream of the oral cavity, including the oropharynx region. Conclusion: Results from this study suggest that key mechanisms underpinning the working principles of inhaler resistance are intricately connected to their complex interaction with the pharynx geometry, which affects the local pressure, local variation in velocity and kinetic energy profile in the airway

Numerical analysis of airflow and particle deposition in multi-fidelity designs of nasal replicas following nasal administration

Background and Objective: An improved understanding of flow behaviour and particle deposition in the human nasal airway is useful for optimising drug delivery and assessing the implications of pollutants and toxin inhalation. The geometry of the human nasal cavity is inherently complex and presents challenges and manufacturing constraints in creating a geometrically realistic replica. Understanding how anatomical structures of the nasal airway affect flow will shed light on the mechanics underpinning flow regulation in the nasal pharynx and provide a means to interpret flow and particle deposition data conducted in a nasal replica or model that has reduced complexity in terms of their geometries. This study aims to elucidate the effects of sinus and reduced turbinate length on nasal flow and particle deposition efficiencies. Methods: A complete nasal airway with maxillary sinus was first reconstructed using magnetic resonance imaging (MRI) scans obtained from a healthy human volunteer. The basic model was then modified to produce a model without the sinus, and another with reduced turbinate length. Computational fluid dynamics (CFD) was used to simulate flow in the nasal cavity using transient flow profiles with peak flow rates of 15 L/min, 35 L/min and 55 L/min. Particle deposition was investigated using discrete phase modelling (DPM). Results: Results from this study show that simplifying the nasal cavity by removing the maxillary sinus and curved sections of the meatus only has a minor effect on airflow. By mapping the spatial distribution of monodisperse particles (10 μm) in the three models using a grid map that consists of 30 grids, this work highlights the specific nasal airway locations where deposition efficiencies are highest, as observed within a single grid. It also shows that lower peak flow rates result in higher deposition differences in terms of location and deposition quantity, among the models. The highest difference in particle deposition among the three nasal models is ∼10%, and this is observed at the beginning of the middle meatus and the end of the pharynx, but is only limited to the 15 L/min peak flow rate case. Further work demonstrating how the outcome may be affected by a wider range of particle sizes, less specific to the pharmaceutical industries, is warranted. Conclusion: A physical replica manufactured without sections of the middle meatus could still be adequate in producing useful data on the deposition efficiencies associated with an intranasal drug formulation and its delivery device

Numerical and experimental evaluation of nasopharyngeal aerosol administration methods in children with adenoid hypertrophy

Article no 12390

Neural tissue biomechanics : biomechanics and models of structural neurological disorders

Research interests in biomechanical modeling of the intracranial system and structural neurological disorders have increased in the last two decades. The lack of clarity on the physiology of the intracranial system has resulted in some disparities in these models. The aim of this chapter is to provide a thorough physiological background of the intracranial system, the mechanics of several types of structural neurological disorders that arise when the system is disturbed and outline the benefits in modeling these disorders. This chapter concludes by discussing some of the impending issues that need to be resolved in order to improve our understanding of a diseased intracranial system using computational models.14 page(s

Computational model of the cerebral ventricles in hydrocephalus

Understanding the mechanisms of tissue injury in hydrocephalus is important to shed light on the pathophysiology of this neurostructural disorder. To date, most of the finite element models created to study hydrocephalus have been two-dimensional (2D). This may not be adequate as the geometry of the cerebral ventricles is unique. In this study, a three-dimensional (3D) finite element model of the cerebral ventricles during hydrocephalus is presented. Results from this model show that during hydrocephalus, the periventricular regions experience the highest stress, and stress magnitude is approximately 80 times higher than the cerebral mantle. This suggests that functional deficits observed in hydrocephalic patients could therefore be more related to the damage to periventricular white matter. In addition, the stress field simulated in the tissues based on the 3D model was found to be approximately four times lower than on the 2D model.4 page(s

Unconfined compression of white matter

The porous properties of brain tissue are important for understanding normal and abnormal cerebrospinal fluid flow in the brain. In this study, a poroviscoelastic model was fitted to the stress relaxation response of white matter in unconfined compression performed under a range of low strain rates. A set of experiments was also performed on the tissue samples using a no-slip boundary condition. Results from these experiments demonstrated that the rheological response of the white matter is primarily governed by the intrinsic viscoelastic properties of the solid phase. The permeability of white matter was found to be of the order of 10⁻¹² m⁴/Ns.8 page(s

Simulation Study of Solidification in the Shell-And-Tube Energy Storage System with a Novel Dual-PCM Configuration

This study proposes a novel dual-PCM configuration with outstanding solidification response in a horizontal shell-and-tube energy storage system. To demonstrate that the proposed PCM configuration is superior in its thermal responses, results from a range of numerical simulations are presented and compared between different configurations of dual-PCM. As the melting/solidus point is a crucial factor for the solidification rate, dual PCMs are chosen such that the average of their melting point is equal to the melting point of the single-PCM in the reference case. Additionally, equal-area sectors are considered for all cases to ensure the same quantities of PCMs are compared. The temporal liquid fraction and temperature contours reveal that solidification is delayed in the upper half of the system due to strong natural convection motions. Therefore, a dual-PCM configuration is offered to improve the solidification rate in this region and accelerate the full solidification process. Results show that placing a PCM with a lower solidus point in the lower half or an annulus-shaped zone around the cold tube can save the full recovery time up to 8.51% and 9.36%, respectively. The integration of these two strategies results in a novel and optimum design that saves the solidification time up to 15.09%

Brain tissue mechanical properties – making sense of 5 decades of test data

18 page(s

Simulation Study of Solidification in the Shell-And-Tube Energy Storage System with a Novel Dual-PCM Configuration

This study proposes a novel dual-PCM configuration with outstanding solidification response in a horizontal shell-and-tube energy storage system. To demonstrate that the proposed PCM configuration is superior in its thermal responses, results from a range of numerical simulations are presented and compared between different configurations of dual-PCM. As the melting/solidus point is a crucial factor for the solidification rate, dual PCMs are chosen such that the average of their melting point is equal to the melting point of the single-PCM in the reference case. Additionally, equal-area sectors are considered for all cases to ensure the same quantities of PCMs are compared. The temporal liquid fraction and temperature contours reveal that solidification is delayed in the upper half of the system due to strong natural convection motions. Therefore, a dual-PCM configuration is offered to improve the solidification rate in this region and accelerate the full solidification process. Results show that placing a PCM with a lower solidus point in the lower half or an annulus-shaped zone around the cold tube can save the full recovery time up to 8.51% and 9.36%, respectively. The integration of these two strategies results in a novel and optimum design that saves the solidification time up to 15.09%

Rheological properties of anisotropic tissues at large amplitude oscillatory shear

The mechanical properties of soft biological tissues have been widely investigated over the past five decades [1–5]. Reported measurements of soft biological tissues such as the brain, spinal cord, liver and muscle vary by orders of magnitude, depending on the sample preparation, anisotropy and loading regime. Knowing the accurate mechanical properties of biological tissues is important for many applications, for example car crash testing and simulations require accurate information on how different parts of the body deform due to a combination of loads. Deformation of tissues around prosthetics and artificial limbs are critical in understanding load transfer at interfaces with the body. The recent use of Magnetic Resonance Elastography (MRE) in diagnostic imaging has resulted in a surge of interest in accurate measurements of mechanical properties of tissues [6].2 page(s