Characterizing the Effects of Nasal Prong Interfaces on Aerosol Deposition in a Preterm Infant Nasal Model.

The objective of this study was to characterize the effects of multiple nasal prong interface configurations on nasal depositional loss of pharmaceutical aerosols in a preterm infant nose-throat (NT) airway model. Benchmark in vitro experiments were performed in which a spray-dried powder formulation was delivered to a new preterm NT model with a positive-pressure infant air-jet dry powder inhaler using single- and dual-prong interfaces. These results were used to develop and validate a computational fluid dynamics (CFD) model of aerosol transport and deposition in the NT geometry.

Analysis of Nasal Interface Options for High-Efficiency Aerosol Administration to Preterm Infants.

An infant air-jet dry powder inhaler (DPI) platform has recently been developed that in combination with highly dispersible spray-dried powder formulations can achieve high-efficiency aerosolization with low actuation air volumes. The objective of this study was to investigate modifications to the nasal interface section of this platform to improve the aerosol delivery performance through preterm nose-throat (NT) models. Aerosol delivery performance of multiple nasal interface flow pathways and prong configurations was assessed with two preterm infant NT models.

High-Efficiency Dry Powder Aerosol Delivery to Children: Review and Application of New Technologies.

While dry powder aerosol formulations offer a number of advantages, their use in children is often limited due to poor lung delivery efficiency and difficulties with consistent dry powder inhaler (DPI) usage. Both of these challenges can be attributed to the typical use of adult devices in pediatric subjects and a lack of pediatric-specific DPI development. In contrast, a number of technologies have recently been developed or progressed that can substantially improve the efficiency and reproducibility of DPI use in children including: (i) nose-to-lung administration with small particles, (ii) active positive-pressure devices, (iii) structures to reduce turbulence and jet momentum, and (iv) highly dispersible excipient enhanced growth particle formulations.

Advancement of a Positive-Pressure Dry Powder Inhaler for Children: Use of a Vertical Aerosolization Chamber and Three-Dimensional Rod Array Interface.

Purpose: Available dry powder inhalers (DPIs) have very poor lung delivery efficiencies in children. The objective of this study was to advance and experimentally test a positive-pressure air-jet DPI for children based on the use of a vertical aerosolization chamber and new patient interfaces that contain a three-dimensional (3D) rod array structure.

Methods: Aerosolization performance of different air-jet DPI designs was first evaluated based on a 10 mg powder fill mass of a spray-dried excipient enhanced growth (EEG) formulation.

Development of Dry Powder Inhaler Patient Interfaces for Improved Aerosol Delivery to Children.

The objective of this study was to explore different internal flow passages in the patient interface region of a new air-jet-based dry powder inhaler (DPI) in order to minimize device and extrathoracic aerosol depositional losses using computational fluid dynamics (CFD) simulations. The best-performing flow passages were used for oral and nose-to-lung (N2L) aerosol delivery in pediatric extrathoracic airway geometries consistent with a 5-year-old child. Aerosol delivery conditions were based on a previously developed and tested air-jet DPI device and included a base flow rate of 13.

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

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.

Development of an Inline Dry Powder Inhaler for Oral or Trans-Nasal Aerosol Administration to Children.

Dry powder inhalers (DPIs) offer a number of advantages, such as rapid delivery of high-dose inhaled medications; however, DPI use in children is often avoided due to low lung delivery efficiency and difficulty in operating the device. The objective of this study was to develop a high-efficiency inline DPI for administering aerosol therapy to children with the option of using either an oral or trans-nasal approach. An inline DPI was developed that consisted of hollow inlet and outlet capillaries, a powder chamber, and a nasal or oral interface.

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

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.

High-Efficiency Nose-to-Lung Aerosol Delivery in an Infant: Development of a Validated Computational Fluid Dynamics Method.

Computational fluid dynamics (CFD) provides a powerful tool for developing new high-efficiency aerosol delivery strategies, such as nose-to-lung (N2L) aerosol administration to infants and children using correctly sized aerosols. The objective of this study was to establish numerically efficient CFD solution methods and guidelines for simulating N2L aerosol administration to an infant based on comparisons with concurrent experiments. N2L administration of a micrometer-sized aerosol (mass median aerodynamic diameter [MMAD] = 1.

Use of computational fluid dynamics deposition modeling in respiratory drug delivery.

Introduction: Respiratory drug delivery is a surprisingly complex process with a number of physical and biological challenges. Computational fluid dynamics (CFD) is a scientific simulation technique that is capable of providing spatially and temporally resolved predictions of many aspects related to respiratory drug delivery from initial aerosol formation through respiratory cellular drug absorption.

Areas Covered: This review article focuses on CFD-based deposition modeling applied to pharmaceutical aerosols.

Recommendations for Simulating Microparticle Deposition at Conditions Similar to the Upper Airways with Two-Equation Turbulence Models.

The development of a CFD model, from initial geometry to experimentally validated result with engineering insight, can be a time-consuming process that often requires several iterations of meshing and solver set-up. Applying a set of guidelines in the early stages can help to streamline the process and improve consistency between different models. The objective of this study was to determine both mesh and CFD solution parameters that enable the accurate simulation of microparticle deposition under flow conditions consistent with the upper respiratory airways including turbulent flow.

Development of an infant complete-airway in vitro model for evaluating aerosol deposition.

A complete-airway in vitro model would be very useful for toxicological dosimetry testing and for developing targeted inhaled medications in cases where conducting in vivo experiments are exceedingly difficult, as with infants. The objective of this study was to determine whether packed bed in vitro models, which contain spheres as the primary repeating unit, provide a realistic representation of aerosol deposition in the tracheobronchial region of infant lungs based on computational fluid dynamics (CFD) predictions. The packed bed (PB) CFD model contained an inlet consistent with airway bifurcation B3 (∼lobar bronchi) leading to a spherical array with voids between the spheres forming a divided flow pathway.