Effect of Design on the Performance of a Dry Powder Inhaler Using Computational Fluid Dynamics. Part 1: Grid Structure and Mouthpiece Length

Coates, Matthew; Fletcher, David F.; Chan, Hak‐Kim; Raper, Judy A

doi:10.1002/jps.20201

Cited by 183 publications

(120 citation statements)

References 15 publications

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“…The pressure distribution within the Cyclohaler indicates that the resistance of the device is dependent on the dimension of tangential air inlets, from which about 50% of the pressure is lost. The remainder of the pressure loss is due to the mesh (data not shown), which is consistent with the findings of Coates et al (11). In addition, Fig.…”

Section: Cfd Modeling Of the Cyclohaler And Modified Cyclohaler Devicessupporting

confidence: 91%

“…Computational fluid dynamics (CFD) is an established methodology for predicting the flow properties and the fate of the particulate system in the respiratory tract and inhalation devices (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). For example, Coates et al demonstrated how CFD modeling of the DPI mouthpiece geometry, dispersion grid and air inlet size (11), airflow rate (12), and capsule properties (13) could be used to investigate aerosol performance.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers

Shur

Lee

Adams

et al. 2012

AAPS J

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Abstract. This study investigated the effect of modifying the design of the Cyclohaler on its aerosolization performance and comparability to the HandiHaler at multiple flow rates. The Cyclohaler and HandiHaler were designated as model test and reference unit-dose, capsule-based dry powder inhalers (DPIs), respectively. The flow field, pressure drop, and carrier particle trajectories within the Cyclohaler and HandiHaler were modeled via computational fluid dynamics (CFD). With the goal of achieving in vitro comparability to the HandiHaler, the CFD results were used to identify key device attributes and to design two modifications of the Cyclohaler (Mod 1 and Mod 2), which matched the specific resistance of the HandiHaler but exhibited different cyclonic flow conditions in the device. Aerosolization performance of the four DPI devices was evaluated by using the reference product's capsule and formulation (Spiriva capsule) and a multistage cascade impactor. The in vitro data showed that Mod 2 provided a closer match to the HandiHaler than the Cyclohaler and Mod 1 at 20, 39, and 55 l/min. The in vitro and CFD results together suggest that matching the resistance of test and reference DPI devices is not sufficient to attain comparable aerosolization performance, and the improved in vitro comparability of Mod 2 to the HandiHaler may be related to the greater degree of similarities of the flow rate of air through the pierced capsule (Q c ) and the maximum impact velocity of representative carrier particles (V n ) in the Cyclohaler-based device. This investigation illustrates the importance of enhanced product understanding, in this case through the CFD modeling and in vitro characterization of aerosolization performance, to enable identification and modification of key design features of a test DPI device for achieving comparable aerosolization performance to the reference DPI device.KEY WORDS: computational fluid dynamics; device design; dry powder inhaler; in vitro comparability; in vitro performance.

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Section: Cfd Modeling Of the Cyclohaler And Modified Cyclohaler Devicessupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers

Shur

Lee

Adams

et al. 2012

AAPS J

View full text Add to dashboard Cite

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“…Even though some reverse flow is observed, the absence of large variation velocity fields gives rise to only small turbulence intensity. Both the increases in gas velocity and decreases in reverse flow are stronger on the wafer with good uniformity because of the decreased reverse flow streams from the turbulence [16]. Similar change in flow patterns is also observed using other nozzle angles as shown in Table 2.…”

Section: Resultssupporting

confidence: 68%

Design and Optimization of Chemical Mixing System for Vacuum Chambers Base of Simulation Results

Ünker¹,

Kaplan²,

Çuvalcı³

2015

IJAET

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Computational fluid dynamics (CFD) is widely used in device design to determine gas flow patterns and turbulence levels. CFD is also used to simulate particles and droplets, which are subjected to various forces, turbulence and wall interactions. These studies can now be performed routinely because of the availability of commercial software containing high quality turbulence and particle models. In order to understand how the gas is brought down to wafer, it is necessary to have a knowledge of the gas flow behavior very early in the design spiral of the Tantalum nitride-Atomic layer deposition (TaN-ALD) chamber by undertaking parametric investigation of the interaction effect between gas flow and the funnel structure. This paper presents such a parametric investigation on a generic TaN-ALD chamber using CFD. The results presented have been analyzed for a total of 11 different cases by varying neck and nozzle angles for a process gas. The gas flow was mainly investigated for the nozzle angles of 4.5, 9, 12 and 20 and the film thickness results were compared with numerical flow patterns. CFD simulations using the turbulence model in ANSYS Fluent v.13 are undertaken. The parametric study has demonstrated that CFD is a powerful tool to study the problem of gas flow-structure interaction on funnel and is capable of providing a means of visualizing the path of the gas under different operating conditions.

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“…The momentum of any particle is dependent on the mass and the velocity of the carrier and as the larger particles will have greater mass there will be greater momentum transfer or high impaction to detach the surface particles. Therefore, significant mechanical forces were thought to be produced due to the carrier-carrier collisions or collisions between the carrier particles and the internal walls of the inhaler during aerosolization (Coates, Fletcher, Chan, & Raper, 2004).…”

Section: Formulations With Large Carriermentioning

confidence: 99%

“…The geometry of the inhaler device, an important factor in drug dispersibility, has been reported to affect the extent of collisions occurring between the inhaler wall and the carrier particles (Coates et al, 2004). The nanoparticulate agglomerates that adhered on the large carriers might be detached as a whole, requiring a much lower velocity than the detachment of a single particle because of the significantly higher inertia for the agglomerates (De Boer, Chan, & Price, 2012).…”

Section: Formulations With Large Carriermentioning

confidence: 99%

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

Wang¹

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Cigarette smoking has become one of the leading causes of preventable deaths all over the world, causing a serious threat to human wellbeing and a tremendous economic burden to governments. The currently available treatment options for smoking cessation are not efficient. The pulmonary delivery of drugs by methods such as dry powder inhaler (DPI) has been recognized as one of the most efficient routes of drug delivery to the targeted area. The lung delivery of nicotine in this way would be expected to mimic the effects of tobacco smoking and could significantly reduce the negative health effects of smoking that result from nicotine addiction.The aim of this study is to develop nanoparticles with controlled physicochemical properties using biodegradable polymer of chitosan (CS) loaded with nicotine salt for pulmonary delivery as DPI formulations. The outcomes of this project are expected to be a safe and effective CS-based nicotine formulation for pulmonary delivery to treat nicotine dependence. This thesis specially addresses the research questions: (1) how to develop a feasible process to manufacture the nanoparticles suitable for pulmonary drug delivery using biodegradable polymer of CS containing nicotine salt; (2) how to develop an animal model for pulmonary drug delivery from DPI formulation using a nose-only inhalation device.The current therapeutic options for treatment of smoking addiction have been reviewed, and current advancements of technology in pulmonary drug delivery are summarised. Buccal administration of drugs exhibits a low oral bioavailability, and sublingual tablets and chewing gums can be swallowed before being absorbed.Although nasal spray of nicotine is a fast way to deliver nicotine into the bloodstream, Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery iii the rate of absorption is still not as rapid as cigarette smoking. Therefore, it is proposed that delivery of nicotine with sustained drug release profile direct into the deep lung is likely to more effectively mimic the rapid effects of cigarette smoking on a physiological level, which could eliminate patient craving and allow the tapering of nicotine level over time to improve patients' compliance.Water in oil (w/o) emulsion crosslinking method has been used to fabricate nicotine hydrogen tartrate (NHT)-loaded CS nanoparticles which separate as solid microaggregates. The physicochemical properties of particles are characterized by a series of techniques. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) shows that the prepared particles are spherical in morphology with rough surface after loading CS particles with NHT. Dynamic Light Scattering (DLS)by Zetasizer determined nanoparticle size ranging from 167.6 nm to 411 nm, while DLS by Mastersizer demonstrated that the microaggregates of these nanoparticles are in the respirable range (<5µm). The surface positive charge as measured by zeta potential tends to decrease with increase of mass ratios of NHT to CS, which is in contr...

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Effect of Design on the Performance of a Dry Powder Inhaler Using Computational Fluid Dynamics. Part 1: Grid Structure and Mouthpiece Length

Cited by 183 publications

References 15 publications

Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers

Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers

Design and Optimization of Chemical Mixing System for Vacuum Chambers Base of Simulation Results

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

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