Effect of design on the performance of a dry powder inhaler using computational fluid dynamics. Part 2: Air inlet size

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

doi:10.1002/jps.20603

Cited by 131 publications

(87 citation statements)

References 17 publications

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“…Thus, for the purpose of increasing the likelihood of establishing comparable in vitro performance and in vivo drug deposition, the specific resistance of a test device should be comparable to the reference device. Furthermore, variations in the fluid dynamics of an entrained airflow of DPIs may influence powder dispersion (10). This highlights the significance of modeling and understanding the complex nature of the flow field in the test and reference devices.…”

Section: Introductionmentioning

confidence: 99%

“…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%

See 1 more Smart Citation

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: Introductionmentioning

confidence: 99%

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

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show abstract

“…It can be seen from the Fig.1 that the reverse flow initially decreases after the angle of 9 and then is mostly eliminated with the angle of 12, suggesting the existence of an optimum lid angle. The center line velocity drop is significant when the nozzle angle is 12, so there is less nonuniform film thickness near the center of wafer for this case [18]. But after the nozzle angle of 12 the center line velocity vector becomes significant and the gas velocity near the wafer center rises.…”

Section: Resultsmentioning

confidence: 83%

“…This is because a large velocity gradient is generated due to the sudden expansion in the flow area as the gas flows pass the nozzle. As a result, turbulence is generated and intensifies along the axial location before reaching a fully developed flow [6], [18]. a b 3.3 Effect of funnel lid dimensions on mole fraction of process gas on wafer variation with time Fig.…”

Section: Effect Of Funnel Lid Dimensions On Consumption Flux Of Procementioning

confidence: 99%

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 key barrier for developing a generic or follow-on version of these DPI products is to overcome the complexity associated with DPI device and formulation design, in order to achieve bioequivalence (BE) to the reference (innovator) product. The complex relationship between design of the passive DPI device and physicochemical properties of the powder formulation controls the fluidization, de-aggregation and aerodynamic particle size distribution (APSD) of the emitted dose (ED) (2). This in turn influences regional deposition of drug particles in the lung and, thus, the efficacy and safety of the DPI product (3).…”

Section: Introductionmentioning

confidence: 99%

Effect of Device Design and Formulation on the In Vitro Comparability for Multi-Unit Dose Dry Powder Inhalers

Shur

Saluja

Lee

et al. 2015

AAPS J

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Abstract. The focus of this investigation was to understand the design space to achieve comparable in vitro performance of two multi-unit dose dry powder inhalers (DPIs)-Flixotide® Accuhaler® (reference product) and MultiHaler® (test product). Flow field, pressure drop and particle trajectories within the test and reference DPI devices were modelled via computational fluid dynamics (CFD). Micronized fluticasone propionate (FP) was characterized to determine particle size distribution (PSD), specific surface area (SSA) and surface interfacial properties using cohesive-adhesive balance (CAB). CFD simulations suggested that the pressure drop and airflow velocity in the MultiHaler® were greater than Accuhaler®. Two modified test devices (MOD MH 1 and MOD MH 2) were manufactured with the introduction of by-pass channels in the airflow path, which achieved comparable specific resistance and airflow path between the test and reference devices. Assessment of reference product formulation in modified test devices suggested that MOD MH 2 achieved comparable in vitro performance to the reference product. CAB analysis suggested that adhesion of all FP batches to lactose was different, with batch D showing greatest and batch A least adhesion to lactose. Test DPI formulations were manufactured using four different batches of FP with milled or sieved lactose, and showed that batch A FP formulated with sieved lactose in MOD MH 2 device demonstrated the highest degree of similarity to the Accuhaler® in vitro deposition. Application of CFD modelling and material characterization of formulation raw materials enabled the modification of device and formulation critical material attributes to create an in vitro comparable device/formulation system to the reference product.KEY WORDS: aerosolization; computational fluid dynamics; device design; dry powder inhaler; in vitro comparability; in vitro performance.

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Effect of design on the performance of a dry powder inhaler using computational fluid dynamics. Part 2: Air inlet size

Cited by 131 publications

References 17 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

Effect of Device Design and Formulation on the In Vitro Comparability for Multi-Unit Dose Dry Powder Inhalers

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