Efficient Nose-to-Lung Aerosol Delivery with an Inline DPI Requiring Low Actuation Air Volume

Farkas, Dale; Hindle, Michael; Longest, P. Worth

doi:10.1007/s11095-018-2473-7

Cited by 25 publications

(15 citation statements)

References 41 publications

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“…Systems that would benefit from low air volumes and positive pressure (active) operation with a small particle aerosol include administration during non-invasive and invasive mechanical ventilation (45,46), administration to infants (47) and administration of aerosols to test animals (48)(49)(50). Previous studies by Farkas et al have illustrated active lowvolume DPI delivery of pharmaceutical aerosol simultaneously with low flow nasal cannula (LFNC) therapy (51,52). By using an approximate 10 ml burst of air at a flowrate of 3 LPM, aerosol administration did not interfere with LFNC ventilation support.…”

Section: Discussionmentioning

confidence: 99%

Development of a New Inhaler for High-Efficiency Dispersion of Spray-Dried Powders Using Computational Fluid Dynamics (CFD) Modeling

Longest

Farkas

2019

AAPS J

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Computational fluid dynamics (CFD) modeling offers a powerful tool for the development of drug delivery devices using a first principles approach, but has been underutilized in the development of pharmaceutical inhalers. The objective of this study was to develop quantitative correlations for predicting the aerosolization behavior of a newly proposed dry powder inhaler (DPI). The dose aerosolization and containment (DAC) unit DPI utilizes inlet and outlet air orifices designed to maximize the dispersion of spray dried powders, typically with low air volumes (~ 10 ml) and relatively low airflow rates (~ 3 L/min). Five DAC-unit geometries with varying orifice outlet sizes, configurations, and protrusion distances were considered. Aerosolization experiments were performed using cascade impaction to determine mean device emitted dose (ED) and mass median aerodynamic diameter (MMAD). Concurrent CFD simulations were conducted to predict both flow field-based and particle-based dispersion parameters that captured different measures of turbulence. Strong quantitative correlations were established between multiple measures of turbulence and the experimentally observed aerosolization metrics of ED and MMAD. As expected, increasing turbulence produced increased ED with best case values reaching 85% of loaded dose. Surprisingly, decreasing turbulence produced an advantageous decrease in MMAD with values as low as approximately 1.6 μm, which is in contrast with previous studies. In conclusion, CFD provided valuable insights into the performance of the DAC-unit DPI as a new device including a two stage aerosolization process offering multiple avenues for future enhancements.

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Section: Discussionmentioning

confidence: 99%

Development of a New Inhaler for High-Efficiency Dispersion of Spray-Dried Powders Using Computational Fluid Dynamics (CFD) Modeling

Longest

Farkas

2019

AAPS J

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“…There is a current need for active dry powder inhalers (DPIs) capable of high efficiency aerosolization that can be operated with low volumes (≤ 30 ml) of actuation air. As demonstrated in previous studies, these devices can be used to administer aerosolized medications simultaneously with non-invasive ventilation (NIV) without interfering with gas support (1,2). Due to rapid device actuation (on the order of 0.2 -0.5 s), aerosol administration can be coordinated with the initial phase of inhalation, thereby minimizing environmental losses of the aerosol during exhalation.…”

Section: Introductionmentioning

confidence: 98%

“…Our group has recently reported the development of a low-air-volume DPI operated with approximately 10 ml air volumes for the aerosolization of highly dispersible excipient enhanced growth EEG powders (1,2,7). The main components of these dose aerosolization and containment (DAC) unit DPIs are the inlet orifice(s), containment volume, and outlet orifice(s), which are each designed to maximize emitted dose and aerosol dispersion for different applications.…”

Section: Introductionmentioning

confidence: 99%

“…Using this approach, a large number of design options are available, including the dimensions and shapes of individual components and the interconnection of these components, with the intent of maximizing aerodynamic factors leading to optimized aerosolization. To evaluate some possible design options, we have considered capsule-based devices that use sharpened capillaries to pierce the capsule and form a fixed flow pathway once the device is assembled (1,2,7). Refillable devices are also of interest for lab use and for aerosol exposure experiments with animals (8,9).…”

Section: Introductionmentioning

confidence: 99%

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Use of Computational Fluid Dynamics (CFD) Dispersion Parameters in the Development of a New DPI Actuated with Low Air Volumes

et al. 2019

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Purpose: To determine the predictive power of computational fluid dynamics (CFD)-based dispersion parameters in the development of a new inline DPI that is actuated with low volumes of air.Methods: Four new versions of a dose aerosolization and containment (DAC)-unit DPI were created with varying inlet and outlet orifice sizes and analyzed with results from five previous designs. A concurrent in vitro and CFD analysis was conducted to predict the emitted dose (ED; as a % of loaded dose) and aerosol mass median aerodynamic diameter (MMAD) produced by each device when actuated with 10 ml air bursts. CFD simulations of device operation were used to predict flow field and particle-based dispersion parameters.Results: Comparisons of experimental and CFD results indicated that multiple flow field and particle-based dispersion parameters could be used to predict ED (minimum RMS Error = 4.9%) and MMAD (minimum RMS Error = 0.04 μm) to a high degree of accuracy. Based on experiments, the best overall device produced mean (standard deviation; SD) ED=82.9(4.3)% and mean MMAD (SD)=1.73(0.07)μm, which were in close agreement with the CFD predictions. Conclusions:A unique relationship was identified in the DAC-unit DPI in which reducing turbulence also reduced the MMAD.

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“…Our group has developed a series of high efficiency air-jet DPIs that are operated with 10 ml of air (via a syringe) (7)(8)(9). These air-jet DPIs use small-gauge hollow capillaries that pierce a powder-containing capsule as part of loading the device, and serve as the air inlet and aerosol outlet.…”

Section: Introductionmentioning

confidence: 99%

Optimizing Aerosolization Using Computational Fluid Dynamics in a Pediatric Air-Jet Dry Powder Inhaler

2019

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The objective of this study was to optimize the performance of a high efficiency pediatric inhaler, referred to as the pediatric air-jet DPI, using computational fluid dynamics (CFD) simulations with supporting experimental analysis of aerosol formation. The pediatric air-jet DPI forms an internal flow pathway consisting of an inlet jet of high-speed air, capsule chamber containing a powder formulation, and outlet orifice. Instead of simulating full breakup of the powder bed to an aerosol in this complex flow system, which is computationally expensive, flow-field-based dispersion parameters were sought that correlated with experimentally determined aerosolization metrics. For the pediatric air-jet DPI configuration that was considered, mass median aerodynamic diameter (MMAD) directly correlated with input turbulent kinetic energy normalized by actuation pressure and flow kinetic energy. Emitted dose (ED) correlated best with input flow rate multiplied by the ratio of capillary diameters. Based on these dispersion parameters, an automated CFD process was used over multiple iterations of over 100 designs to identify optimal inlet and outlet capillary diameters, which affected system performance in complex and unexpected ways. Experimental verification of the optimized designs indicated an MMAD <1.6 μm and an ED >90% of loaded dose. While extrathoracic depositional loss will be determined in future studies, at an operating flow rate of 15 LPM it is expected that pediatric mouth-throat or even nose-throat aerosol deposition fractions will be below 10% and potentially less than 5% representing a significant improvement in the delivery efficiency of dry powder pharmaceutical aerosols to children.

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Efficient Nose-to-Lung Aerosol Delivery with an Inline DPI Requiring Low Actuation Air Volume

Abstract: The optimized LV-DPI system is capable of high efficiency lung delivery of powder aerosols through a challenging nasal cannula interface.

Cited by 25 publications

References 41 publications

Development of a New Inhaler for High-Efficiency Dispersion of Spray-Dried Powders Using Computational Fluid Dynamics (CFD) Modeling

Development of a New Inhaler for High-Efficiency Dispersion of Spray-Dried Powders Using Computational Fluid Dynamics (CFD) Modeling

Use of Computational Fluid Dynamics (CFD) Dispersion Parameters in the Development of a New DPI Actuated with Low Air Volumes

Optimizing Aerosolization Using Computational Fluid Dynamics in a Pediatric Air-Jet Dry Powder Inhaler

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