Mouth-throat Deposition Research Articles

In Vitro and In Silico Investigations on Drug Delivery in the Mouth-Throat Models with Handihaler®.

This work aimed to evaluate the relative inhalation parameters that affect the deposition of inhaled aerosols, including mouth-throat morphology, airflow rate, and initial condition of emitted particles. In vitro experiments were conducted using the US Pharmacopeia (USP) throat and a realistic mouth-throat (RMT) with Handihaler®. Then, in silico study of the gas-solid flow was performed by computational fluid dynamics and discrete phase method. Results indicated that aerosol deposition in RMT was higher compared to that in USP throat at an airflow rate of 30 L/min, with 33.16 ± 7.84% and 21.11 ± 7.1% lung deposition in USP throat and RMT models, respectively, which showed a better correlation with in vivo data from the literature. Increasing airflow rate resulted in better drug aerosolization, while the fine particle dose trend ascended before declining, with the peak value obtained at a flow rate of 40 L/min. Overall, the effect of geometrical variation was more significant. Additionally, in silico results demonstrated clearly that the initial conditions of the emitted particles from inhalers affected the subsequent deposition. Larger momentum possessed by the central aerosol jet entering the mouth directly led to stronger impaction, which resulted in the deposition in the front region of mouth-throat models. This study is beneficial to develop an in silico method to understand the underlying mechanisms of in vivo mouth-throat deposition.

A CFD Investigation on the Aerosol Drug Delivery in the Mouth–Throat Airway Using a Pressurized Metered-Dose Inhaler Device

Inhalation therapy involving a pressurized metered-dose inhaler (pMDI) is one of the most commonly used and effective treatment methods for patients with asthma. The purpose of this study was to develop a computational fluid dynamics (CFD) model to characterize aerosol flow issued from a pMDI into a simulated mouth–throat geometry. The effects of air flow rate and cone angle were analyzed in detail. The behaviour of the multiphase flow initiated at the inhaler actuation nozzle and extended through the mouth–throat airway was simulated based on the Eulerian-Lagrangian discrete phase model, with the k-ω model applied for turbulency. We validated our model against published experimental measurements and cover the hydrodynamic aspect of the study. The recirculation we observed at the 90° bend inside the mouth–throat airway resulted in the selective retention of larger diameter particles, and the fluid flow patterns were correlated with drug deposition behaviour. Enhancing air flow rates up to three times reduced the aerodynamic particle diameters to 20%. We also observed that, as cone angle increased, mouth deposition increased; an 8° cone angle was the best angle for the lowest mouth–throat deposition.

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

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. Aerosolization performance of different air-jet DPI designs was first evaluated based on a 10mg powder fill mass of a spray-dried excipient enhanced growth (EEG) formulation. Devices were actuated with positive pressure using flow rate (10-20L/min) and inhaled volume (750ml) conditions consistent with a 5-year-old child. Devices with best performance were connected to different mouthpiece designs to determine the effect on aerosolization and tested for aerosol penetration through a realistic pediatric in vitro mouth-throat model. Use of the new vertical aerosolization chamber resulted in high quality aerosol formation. Inclusion of a 3D rod array structure in the mouthpiece further reduced aerosol size by approximately 20% compared to conditions without a rod array, and effectively dissipated the turbulent jet leaving the device. Best case device and mouthpiece combinations produced < 2% mouth-throat depositional loss and > 70% lung delivery efficiency based on loaded dose. In conclusion, use of a 3D rod array in the MP of a positive-pressure air-jet DPI was found to reduce aerosol size by 20%, not significantly increase MP depositional loss, reduce mouth-throat deposition by 6.4-fold and enable lung delivery efficiency as high as 73.4% of loaded dose based on pediatric test conditions.

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 13.3 LPM (delivered from a small ventilation bag) and an inhaled air volume of 750mL. Initial CFD models of the system clearly established that deposition on either the back of the throat or nasal cannula bifurcation was strongly correlated with the maximum velocity exiting the flow passage. Of all designs tested, the combination of a 3D rod array and rapid expansion of the flow passage side walls was found to dramatically reduce interface and device deposition and improve lung delivery of the aerosol. For oral aerosol administration, the optimal flow passage compared with a base case reduced device, mouthpiece, and mouth-throat deposition efficiencies by factors of 8-, 3-, and 2-fold, respectively. For N2L aerosol administration, the optimal flow pathway compared with a base case reduced device, nasal cannula, and nose-throat deposition by 16-, 6-, and 1.3-fold, respectively. In conclusion, a new patient interface design including a 3D rod array and rapid expansion dramatically improved transmission efficiency of a dry powder aerosol.

Spacer, Aerosol Therapy through Space and Time

Within this review, results of a literature analysis on the application of spacers with pressurized metered dose inhalers (pMDI) are described and evaluated. Next to an extensive revision on effects of spacers, the impacts of current guidelines and the conditions for product authorisations on the use of spacers are described which result from the interplay of characteristics from dose inhalers with a spacer. Spacers are generally useful to avoid coordination problems concerning the actuation of a pMDI at the beginning of an inhalation. Furthermore, in comparison to the pMDI application without a spacer a reduced mouth-throat deposition is applicable to all pMDI spacer combinations. However, some new pMDI release the aerosol in a quality that may not necessarily require a spacer to avoid a high drug deposition in the mouth-throat area as the aerosol quality will not be greatly improved with a spacer. The delivered mass of the active ingredient as well as the aerosol quality released from a spacer vary substantially with the use of different spacers. A change of spacer while using the same dose inhaler can maximally result in a doubling or halving of the quantity of the active ingredient applied. These facts are nowadays considered by the European regulatory agency. If a spacer application is intended for pMDIs that were developed and approved after 2009, the correspondent SMP (Summary of Product Characteristics) should at least make one specific recommendation for a spacer that should be based upon relevant in vitro data or additional in vivo data. If a different spacer than the recommended one is used, the effectively applied dose cannot be correctly anticipated. This should be considered when choosing a spacer.

Evaluation of Bio-relevant Mouth-Throat Models for Characterization of Metered Dose Inhalers.

For inhalation drug characterization, the traditionally used USP induction port provides limited in vivo predictive capability because it does not adequately mimic airway geometry. In this study, various bio-relevant mouth-throat (MT) models, including Alberta Idealized Throat (AIT), and 3D printed large/medium/small-sized VCU (Virginia Commonwealth University) models were evaluated using two metered dose inhaler (MDI) drug products: a solution MDI containing beclomethasone dipropionate (BDP-MDI) and a suspension MDI containing fluticasone propionate (FP-MDI). For BDP-MDI, use of VCU large and small MT models resulted in a significantly higher MT deposition and lower fine particle fraction (FPF) compared with the other MT models. In the case of FP-MDI, the three VCU models resulted in higher MT deposition and lower FPF compared with the USP induction port and AIT. Overall, the in vitro testing results for the suspension MDI were more sensitive to geometric differences of the MT models than those for the solution MDI. Our results suggest that in vitro characterization of MDI products can be influenced by many factors, including the type of formulation, the MT geometry, shape, internal space volume, and the material used to make the MT models.

Spacer, Aerosol Therapy through Space and Time

Aim of the literature review Within this review, results of a literature analysis on the application of spacers with pressurized metered dose inhalers (pMDI) are described and evaluated. Methods Next to an extensive revision on effects of spacers, the impacts of current guidelines and the conditions for product authorisations on the use of spacers are described which result from the interplay of characteristics from dose inhalers with a spacer. Results Spacers are generally useful to avoid coordination problems concerning the actuation of a pMDI at the beginning of an inhalation. Furthermore, in comparison to the pMDI application without a spacer a reduced mouth-throat deposition is applicable to all pMDI spacer combinations. However, some new pMDI release the aerosol in a quality that may not necessarily require a spacer to avoid a high drug deposition in the mouth-throat area as the aerosol quality will not be greatly improved with a spacer. The delivered mass of the active ingredient as well as the aerosol quality released from a spacer vary substantially with the use of different spacers. A change of spacer while using the same dose inhaler can maximally result in a doubling or halving of the quantity of the active ingredient applied. These facts are nowadays considered by the European regulatory agency. Conclusion If a spacer application is intended for pMDIs that were developed and approved after 2009, the correspondent SMP (Summary of Product Characteristics) should at least make one specific recommendation for a spacer that should be based upon relevant in vitro data or additional in vivo data. If a different spacer than the recommended one is used, the effectively applied dose cannot be correctly anticipated. This should be considered when choosing a spacer.

Parametric study on mouth–throat geometrical factors on deposition of orally inhaled aerosols

There is a growing need to select a realistic mouth–throat (MT) model to replace the USP induction port (IP) which underestimates MT deposition of inhaled particles. Even though there are many image-based MT models in literature, substantial inconsistencies exist regarding the critical geometrical factors that affect the MT deposition. The objective of this study was to systematically evaluate the relative importance of MT geometrical factors that affect the deposition of orally inhaled aerosols, which include the oral cavity volume, glottis area, airway curvature, and MT airway volume. Four existing MT models with different level of complexities were implemented. HyperWorks was used to vary the dimensions of the geometrical factors. For each factor, five variants were studied in each airway model. A well-validated fluid–particle transport model was used to simulate the airflow and particle deposition. The geometrical-factor-induced deposition variations were analyzed using ANOVA to determine the relative influence of each factor on particle deposition in the MT airway. Results showed that the realism of airway models significantly affected the MT deposition, and the USP IP underestimated the realistic model by up to 55%. The glottis area and total airway volume were found to be the two most predominant factors (both p values<0.01). Replacing the USP IP 90° elbow with curved bends significantly reduced the deposition. However, the MT airway curvature in the other three models had insignificant effects. The effect of the oral cavity volume was also found to be insignificant. Results of this study can provide guidance in developing or selecting a representative MT model to replace the conventional USP IP. A realistic glottis area should be retained in future computational and in vitro deposition studies.

Effect of Induced Charge on Deposition of Uniformly Charged Particles in a Pediatric Oral-Extrathoracic Airway

An in vitro study was conducted in the Alberta idealized child mouth-throat, which mimics average deposition in a set of nine 6–14-year-old subjects, to examine the enhancement of deposition of monodisperse uniformly charged particles as a result of induced electrostatic forces. A purpose-based atomizer was designed and built for generating monodisperse, uniformly charged particles. The atomizer generates droplets by jet break up under the action of capillary waves and charges them via electrostatic induction. The experiments cover different particle aerodynamic diameters (d a = 3.6, 4.4, and 5.9 μm), at two flow rates (Q = 10 and 20 L/min), over a wide range of elementary charges per particle (0–10,000 e). The results show substantial increases in particle deposition in the present idealized pediatric mouth throat compared to neutral aerosols. Two empirical equations, as a function of Reynolds number, Stokes number, and induced charge number are introduced for the prediction of mouth-throat deposition in...

Aerosolization characteristics of dry powder inhaler formulations for the excipient enhanced growth (EEG) application: Effect of spray drying process conditions on aerosol performance

The aim of this study was to develop a spray dried submicrometer powder formulation suitable for the excipient enhanced growth (EEG) application. Combination particles were prepared using the Buchi Nano spray dryer B-90. A number of spray drying and formulation variables were investigated with the aims of producing dry powder formulations that were readily dispersed upon aerosolization and maximizing the fraction of submicrometer particles. Albuterol sulfate, mannitol, L-leucine, and poloxamer 188 were selected as a model drug, hygroscopic excipient, dispersibility enhancer and surfactant, respectively. Formulations were assessed by scanning electron microscopy and aerosol performance following aerosolization using an Aerolizer dry powder inhaler (DPI). In vitro drug deposition was studied using a realistic mouth-throat (MT) model. Based on the in vitro aerosolization results, the best performing submicrometer powder formulation consisted of albuterol sulfate, mannitol, L-leucine and poloxamer 188 in a ratio of 30:48:20:2, containing 0.5% solids in a water:ethanol (80:20%, v/v) solution which was spray dried at 70 °C. The submicrometer particle fraction (FPF(1 μm/ED)) of this final formulation was 28.3% with more than 80% of the capsule contents being emitted during aerosolization. This formulation also showed 4.1% MT deposition. The developed combination formulation delivered a powder aerosol developed for the EEG application with high dispersion efficiency and low MT deposition from a convenient DPI device platform.

In Vitro Investigation of the Effect of Ambient Humidity on Regional Delivered Dose with Solution and Suspension MDIs

Existing literature has shown that high relative humidity (RH) affects in vitro aerosol drug delivery of nebulizer and pressurized metered dose inhaler (pMDI) formulations. The aim of this study is to investigate in vitro mouth-throat deposition and lung delivery of selected solution and suspension pMDI formulations, under a range of RH, temperature, and flow rate conditions. The Alberta Idealized Throat was connected to a collection filter and placed in an environmental control chamber. The formulations selected were beclomethasone dipropionate (BDP) in 13% w/w ethanol/1.3% w/w glycerol and HFA-134a propellant solution ("BDP HFA134a"), BDP in 13% w/w ethanol and HFA-227 propellant solution ("BDP HFA227"), and Flixotide Evohaler (fluticasone propionate 250 μg/dose in HFA-134a suspension). Each of these pMDI formulations was dispersed into the mouth-throat and filter assembly in triplicate, according to an experimental matrix consisting of the following conditions: air flow rates of 28.3, 60, and 90 L/min; 0%, 35%, and 80% RH; operating temperatures of 20°C and 40°C. There was a general increase in mouth-throat deposition and corresponding decrease in filter deposition (representing lung dose fraction), with increasing RH for both BDP HFA134a and Flixotide pMDIs. Increasing temperature from 20°C to 40°C resulted in decreased mouth-throat deposition and increased lung dose fraction for the solution pMDIs, but generally no effect for the suspension pMDI. Not only is the dose delivery of pMDI formulations affected by environmental conditions (in some cases causing up to 50% reduction in lung delivery), but solution and suspension formulations also behave differently in response to these conditions. These results have implications during dosage form design, testing, and for usage patient use.

In Vitro Tests for Aerosol Deposition. III: Effect of Inhaler Insertion Angle on Aerosol Deposition

Inhaler orientation with respect to a patient's mouth may be an important variable determining the efficiency of aerosol lung delivery. The effect of insertion angle on regional deposition was evaluated for a series of inhalers using concurrent in vitro and computational fluid dynamics (CFD) analysis. Geometrically realistic physical mouth-throat (MT) and upper tracheobronchial (TB) models were constructed to connect different inhalers at a series of insertion angles relative to the horizontal plane of the model. These models were used to assess albuterol sulfate deposition from the Novolizer(®) dry powder inhaler (DPI), Proventil(®) HFA pressurized metered dose inhaler (MDI), and Respimat(®) Soft Mist™ Inhaler (SMI) following the actuation of a single dose. Drug deposition from Novolizer DPI was studied for Salbulin(®) and an experimental "drug only" formulation. Albuterol sulfate was recovered and quantified from the device and the MT and TB regions. Significant differences in MT and total lung dose (TLD) of albuterol sulfate deposition were not observed for Salbulin Novolizer DPI and Respimat SMI inserted at different angles. In contrast, drug-only Novolizer DPI and Proventil HFA MDI showed a significant difference in MT and TLD deposition using different insertion angles. For drug-only Novolizer DPI and Proventil HFA MDI, the lowest and the highest MT depositions were observed at +10° and -20°, respectively; for Respimat SMI and Salbulin Novolizer DPI, these angles were -10° and +10°, and +20° and -20°, respectively. CFD simulations were in agreement with the experimental results and illustrated shifts in local particle deposition associated with changes in insertion angle. The effect of inhaler orientation at the inhaler-mouth interface on MT aerosol deposition appeared to be dependent on velocity, aerosol size, and formulation. These findings not only demonstrate the need for patient education on correct inhaler orientation, but provide important new methods for those designing new inhalers.

Performance of Combination Drug and Hygroscopic Excipient Submicrometer Particles from a Softmist Inhaler in a Characteristic Model of the Airways

Excipient enhanced growth (EEG) of inhaled submicrometer pharmaceutical aerosols is a recently proposed method intended to significantly reduce extrathoracic deposition and improve lung delivery. The objective of this study was to evaluate the size increase of combination drug and hygroscopic excipient particles in a characteristic model of the airways during inhalation using both in vitro experiments and computational fluid dynamic (CFD) simulations. The airway model included a characteristic mouth-throat (MT) and upper tracheobronchial (TB) region through the third bifurcation and was enclosed in a chamber geometry used to simulate the thermodynamic conditions of the lungs. Both in vitro results and CFD simulations were in close agreement and indicated that EEG delivery of combination submicrometer particles could nearly eliminate MT deposition for inhaled pharmaceutical aerosols. Compared with current inhalers, the proposed delivery approach represents a 1-2 order of magnitude reduction in MT deposition. Transient inhalation was found to influence the final size of the aerosol based on changes in residence times and relative humidity values. Aerosol sizes following EEG when exiting the chamber (2.75-4.61μm) for all cases of initial submicrometer combination particles were equivalent to or larger than many conventional pharmaceutical aerosols that frequently have MMADs in the range of 2-3μm.

CFD simulations of enhanced condensational growth (ECG) applied to respiratory drug delivery with comparisons to in vitro data

Enhanced condensational growth (ECG) is a newly proposed concept for respiratory drug delivery in which a submicrometer aerosol is inhaled in combination with saturated or supersaturated water vapor. The initially small aerosol size provides for very low extrathoracic deposition, whereas condensation onto droplets in vivo results in size increase and improved lung retention. The objective of this study was to develop and evaluate a CFD model of ECG in a simple tubular geometry with direct comparisons to in vitro results. The length (29 cm) and diameter (2 cm) of the tubular geometry were representative of respiratory airways of an adult from the mouth to the first tracheobronchial bifurcation. At the model inlet, separate streams of humidified air (25, 30, and 39 °C) and submicrometer aerosol droplets with mass median aerodynamic diameters (MMADs) of 150, 560, and 900 nm were combined. The effects of condensation and droplet growth on water vapor concentrations and temperatures in the continuous phase (i.e., two-way coupling) were also considered. For an inlet saturated air temperature of 39 °C, the two-way coupled numerical (and in vitro) final aerosol MMADs for initial sizes of 150, 560, and 900 nm were 1.75 μm (vs. 1.23 μm), 2.58 μm (vs. 2.66 μm), and 2.65 μm (vs. 2.63 μm), respectively. By including the effects of two-way coupling in the model, agreements with the in vitro results were significantly improved compared with a one-way coupled assumption. Results indicated that both mass and thermal two-way coupling effects were important in the ECG process. Considering the initial aerosol sizes of 560 and 900 nm, the final sizes were most influenced by inlet saturated air temperature and aerosol number concentration and were not largely influenced by initial size. Considering the growth of submicrometer aerosols to above 2 μm at realistic number concentrations, ECG may be an effective respiratory drug delivery approach for minimizing mouth–throat deposition and maximizing aerosol retention in a safe and simple manner. However, future studies are needed to explore effects of in vivo boundary conditions, more realistic respiratory geometries, and transient breathing.

Large eddy and detached eddy simulations of fluid flow and particle deposition in a human mouth–throat

Fluid flow was simulated in a human mouth–throat model under normal breathing conditions (30 l/min) alternatively employing RANS k – ω (without near-wall corrections), DES and LES methods. To test the validity of the fluid phase simulations, PIV measurements were carried out in a central sagittal plane of an identical model cast. Velocity and kinetic-energy profiles showed good quantitative agreement of experiments with LES/DES, and less so with RANS k – ω . Mouth–throat deposition was simulated for particle diameters 2, 4, 6, 8 and 10 μ m . By comparison with existing experimental data, LES/DES showed considerable improvement over the RANS k – ω model in predicting deposition for particle sizes below 5 μ m . For the bigger particles, RANS k – ω and LES/DES methods produced similarly good predictions. It is concluded that for the simulation of medication aerosols inhaled at a steady flow rate of 30 l/min, LES and DES provide more accurate results than the RANS k – ω model tested.

Comparison of ambient and spray aerosol deposition in a standard induction port and more realistic mouth–throat geometry

For inhalation aerosols, it is well known that spray momentum and geometry characteristics can significantly influence deposition in the mouth–throat (MT) region. However, little is know about the quantitative influence of spray momentum on aerosol transport and deposition. The objective of this study was to evaluate the effect of spray momentum on deposition in a standard induction port (IP) and a representative MT geometry using capillary-generated aerosols. Capillary aerosol generation (CAG) was selected as a model spray aerosol system that has not been previously tested in a realistic throat geometry. To evaluate the effects of spray momentum, the transport and deposition characteristics of transient capillary-generated aerosols were compared with ambient particles of the same size inhaled at a steady flow rate of 30 L/min. To evaluate the influence of geometry, aerosols were considered in a standard IP and a more realistic MT model. A previously tested CFD model was employed to simulate aerosol transport and deposition for ambient and CAG spray aerosols in both the IP and MT geometries. Considering the capillary-generated spray, good agreement was observed for the deposition of drug mass between the in vitro experiments (IP—15.3%, MT—19.4%) and CFD model predictions without droplet evaporation (IP—14.7%, MT—20.8%). In all cases considered, deposition was increased for spray vs. ambient aerosols and in the MT geometry vs. the IP model. Based on CFD results for a representative polydisperse aerosol distribution, the deposition of ambient particles was highly sensitive to the geometry considered, with 2.9 times more deposition in the MT compared to the IP model. In contrast, deposition was less influenced by the geometry for a CAG spray aerosol, with only a 25–40% deposition increase in the MT. As a result, use of the simple IP model may provide a reasonable approximation of total MT deposition for systems with high spray momentum. However, the IP model may be less useful for evaluating the total MT deposition in systems with reduced spray momentum effects.

In Vivo–In Vitro Comparison of Deposition in Three Mouth–Throat Models with Qvar® and Turbuhaler® Inhalers

In vitro polydisperse aerosol deposition in three mouth-throat models, namely, the USP (United States Pharmacopeia) mouth-throat (induction port), idealized mouth-throat, and highly idealized mouth-throat, was investigated experimentally. Aerosol particles emitted from two commercial inhalers, Qvar (pMDI) and Turbuhaler (DPI), were used. The in vitro deposition results in these three mouth-throat models were compared with in vivo data available from the literature. For the DPI, mouth-throat deposition was 57.3 +/- 4.5% for the USP mouth-throat, 67.8 +/- 2.2% for the idealized mouth-throat, and 69.3 +/- 1.1% for the highly idealized mouth-throat, which are all relatively close to the in vivo value of 65.8 +/- 10.1%. In contrast, for the pMDI, aerosol deposition in the idealized mouth-throat (25.8 +/- 4.2%) and the highly idealized mouth-throat (24.9 +/- 2.8%) agrees with the in vivo data (29.0 +/- 18.0%) reported in the literature better than that for the USP mouth-throat (12.2 +/- 2.7%). In both cases, the USP mouth-throat gives the lowest deposition among the three mouth-throat models studied. In summary, both the idealized mouth-throat and highly idealized mouth-throat improve the accuracy of predicted mean in vivo deposition in the mouth-throat region. This result hints at the potential applicability of either the idealized mouth-throat or highly idealized mouth-throat as a future USP mouth-throat standard to provide mean value prediction of in vivo mouth-throat deposition.

Modeling of Aerosol Deposition with Interface Devices

Various approaches can be used to mathematically model the performance of different masks, mouthpieces, and aerosol delivery devices. The sophistication of such models can vary widely, from the use of simple algebraic empirical correlations to advanced computational fluid dynamics simulations. Bench-top testing is also often used to model aspects of devices, since it is difficult to capture certain aspects of device behavior with mathematical models. These various approaches to modeling differ in their limitations. Empirical correlations exist for predicting the effects of varying mouthpiece diameter and mouth-throat dimensions on extrathoracic losses, but are restricted to stable, nonballistic aerosols in certain flow rate ranges. Computational fluid dynamics (CFD) simulations that solve the Reynolds-averaged Navier-Stokes (RANS) equations typically require near-wall turbulence corrections in order to adequately model mouth-throat deposition, while Large Eddy Simulation (LES) removes this deficiency. Bench-top models that use replicas of the extrathoracic airways vary in their accuracy and generality in replicating the filtering properties of these airways. Choosing and using these various modeling approaches for evaluating patient-device interfaces requires knowledge of their merits and pitfalls, a brief discussion of which is given here.

A Dry Powder Inhaler with Reduced Mouth–Throat Deposition

A novel, compact, and highly efficient dry powder inhaler (DPI) with low mouth-throat deposition is described. The performance of this DPI was evaluated by measuring both (1) the total aerosol deposition in and distal to an idealized mouth-throat cast and (2) the fine particle fraction (FPF) using a standard Mark II Anderson impactor. Ultraviolet (UV) spectroscopy techniques were used in the aerosol deposition measurements. Two inhalation aerosol powders, namely budesonide (extracted from a Pulmicort/Turbuhaler multi-dose device, 200 microg/dose) and ciprofloxacin + lipid + lactose (in-house), were dispersed by the DPI at a steady inhalation flow rate of 60 L/min. The newly developed DPI had a total aerosol delivery distal to the mouth-throat cast of 50.5% +/- 3.04% and 69.7% +/- 1.5% for the budesonide and ciprofloxacin + lipid + lactose aerosols, respectively. This is a significant improvement over the Turbuhaler original device delivery of 34.5% +/- 5.2%, particularly considering that in vitro mouth-throat deposition dropped from 27.5% +/- 5.4% with the budesonide Turbuhaler to 11.0% +/- 3.5% with the present inhaler. The different lung deliveries from the same inhaler for the two formulations above also confirm that the overall performance of an inhaler is optimizable via powder formulations.

Experimental Measurement and Numerical Study of Particle Deposition in Highly Idealized Mouth-Throat Models

Particle deposition in the human mouth-throat is an important factor in evaluating efficiency of drug delivered by inhalation devices, such as pMDIs or DPIs. Current USP standard impactor induction ports (which serve as an in vitro representative of the adult mouth-throat) underpredict in vivo mouth-throat deposition. However, preliminary experimental data in the prototype geometry of a highly idealized mouth-throat has indicated that it is a promising replacement for the USP mouth-throat (Zhang et al. 2004). In this study, partial optimization design of the highly idealized mouth-throat was performed using computational fluid dynamics (CFD) simulations. The performance of six candidate highly idealized mouth-throat geometries, each with a straight tube inlet of inner diameter 17.3 mm, was evaluated experimentally by measuring monodisperse particle deposition efficiency. Gravimetry was used to determine particle deposition in these geometries. Monodisperse particles of di-2-ethylhexyl-sebecate (DEHS) oil ...