Induction Port Research Articles

Exploring the impact of sample flowrate on in vitro measurements of metered dose inhaler performance

Pharmacopoeial methods for measurement of the aerodynamic particle size distribution (APSD) of metered dose inhalers (MDIs) by cascade impaction specify a sampling flow rate of 28.3L/min. However, there is little data within the literature to rationalize this figure, or to support its clinical relevance. In addition, the standard United States Pharmacopoeia Induction Port (USP IP) used for testing is known to inaccurately reflect deposition behavior in the upper airway, further compromising the relevance of testing, for product development.This article describes experimental studies of the effect of sampling flow rate on APSD data gathered using an Andersen Cascade Impactor (ACI). Tests were carried out using two different formulations to assess the influence of formulation composition. In addition, comparative testing with an Alberta Idealised Throat, in place of the USP IP, to ensure more realistic representation of the upper airway.The results show how measured APSD and fine particle dose, the dose than on the basis of size would be expected to deposit in the lung, vary as a function of test methodology, providing insight as to how the testing can be modified towards greater clinical relevance.

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.

Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals

Rodents are routinely used in inhalation toxicology tests as human surrogates. However, in vitro dosimetry tests in rodent casts are still scarce due to small rodent airways and in vitro tests to quantify sub-regional dosimetry are still impractical. We hypothesized that for inertial particles whose deposition is dominated by airflow convection (Reynolds number) and particle inertia (Stokes number), the deposition should be similar among airway replicas of different scales if their Reynolds and Stokes numbers are kept the same. In this study, we aimed to (1) numerically test the hypothesis in three airway geometries: a USP induction port, a human nose model, and a Sprague-Dawley rat nose model, and (2) find the range of applicability of this hypothesis. Five variants of the USP and human nose models and three variants of the rat nose model were tested. Inhalation rates and particle sizes were scaled to match the Reynolds number and Stokes numbers. A low-Reynolds-number k–ω model was used to resolve the airflow and a Lagrangian tracking algorithm was used to simulate the particle transport and deposition. Statistical analysis of predicted doses was conducted using ANOVA. For normal inhalation rates and particle diameters ranging from 0.5 to 24µm, the deposition differences between the life-size and scaled models are insignificant for all airway geometries considered (i.e., human nose, USP, and rat nose). Furthermore, the deposition patterns and exit particle profiles also look similar among scaled models. However, deposition rates and patterns start to deviate if inhalation rates are too low, or particle sizes are too large. For the rat nose, the threshold velocity was found to be 0.71m/s and the threshold Froude number to be 50. Results of this study provide a theoretical foundation for sub-regional in vitro dosimetry tests in small animals and for interpretation of data from inter-species or intra-species with varying body sizes.

Multivariate Analysis of Effects of Asthmatic Patient Respiratory Profiles on the In Vitro Performance of a Reservoir Multidose and a Capsule-Based Dry Powder Inhaler

PurposeThe aim of this work was to evaluate the effect of two different dry powder inhalers, of the NGI induction port and Alberta throat and of the actual inspiratory profiles of asthmatic patients on in-vitro drug inhalation performances.MethodsThe two devices considered were a reservoir multidose and a capsule-based inhaler. The formulation used to test the inhalers was a combination of formoterol fumarate and beclomethasone dipropionate. A breath simulator was used to mimic inhalatory patterns previously determined in vivo. A multivariate approach was adopted to estimate the significance of the effect of the investigated variables in the explored domain.ResultsBreath simulator was a useful tool to mimic in vitro the in vivo inspiratory profiles of asthmatic patients. The type of throat coupled with the impactor did not affect the aerodynamic distribution of the investigated formulation. However, the type of inhaler and inspiratory profiles affected the respirable dose of drugs.ConclusionsThe multivariate statistical approach demonstrated that the multidose inhaler, released efficiently a high fine particle mass independently from the inspiratory profiles adopted. Differently, the single dose capsule inhaler, showed a significant decrease of fine particle mass of both drugs when the device was activated using the minimum inspiratory volume (592 mL).

Abstracts from The Aerosol Society Drug Delivery to the Lungs 25Edinburgh International Conference Centre Edinburgh, Scotland, UK December 10–12, 2014

Abstracts from The Aerosol Society Drug Delivery to the Lungs 25Edinburgh International Conference Centre Edinburgh, Scotland, UK December 10–12, 2014

De-agglomeration Effect of the US Pharmacopeia and Alberta Throats on Carrier-Based Powders in Commercial Inhalation Products.

The US pharmacopeia (USP) and Alberta throats were recently reported to cause further de-agglomeration of carrier-free powders emitted from some dry powder inhalers (DPIs). This study assessed if they have similar influences on commercially available carrier-based DPIs. A straight tube, a USP throat, and an Alberta throat (non-coated and coated) were used for cascade impaction testing. Aerosol fine particle fraction (FPF ≤ 5μm) was computed to evaluate throat-induced de-agglomeration. Computational fluid dynamics are employed to simulate airflow patterns and particle trajectories inside the USP and Alberta throats. For all tested products, no significant differences in the in vitro aerosol performance were observed between the USP throat and the straight tube. Using fine lactose carriers (<10μm), Symbicort(®) and Oxis(™) showed minimal impaction inside the Alberta throat and resulted in similar FPF among all induction ports. For products using coarse lactose carriers (>10μm), impaction frequency and energy inside the Alberta throat were significant. Further de-agglomeration was noted inside the non-coated Alberta throat for Seretide(®) and Spiriva(®), but agglomerates emitted from Relenza(®), Ventolin(®), and Foradil(®) did not further break up into smaller fractions. The coated Alberta throat considerably reduced the FPF values of these products due to the high throat retention, but they generally agreed better with the in vivo data. In conclusion, depending on the powder formulation (including carrier particle size), the inhaler, and the induction port, further de-agglomeration could happen ex-inhaler and create differences in the in vitro measurements.

168 Combining inhalation by a breath-actuated nebulizer (BAN) and exhalation with oscillating positive expiratory pressure device (OPEP) offers potential for simultaneous therapy: A laboratory study

Objectives Mobilization of secretions by OPEP is often given separately to aerosol delivery. Combining a nebulizer [AeroEclipse®-II, Trudell Medical International (TMI)] with OPEP (Aerobika*, TMI), both therapies can be delivered concurrently. We investigated if the BAN output is affected by use with the Aerobika* device, or by substituting another OPEP product (acapella® duet, Smiths Medical). Methods A Next Generation Cascade Impactor operated at 15 L/min was used in accordance with United States Pharmacopeia (USP) ‘Products for Nebulization' to make droplet size measurements of the BAN-aerosol (3×3 replicates/device) operated by compressed air at 50 psig. The BAN was filled with 4 mL ipratropium bromide anticholinergic solution (0.5 mg/ml, TEVA), and connected directly to the USP induction port. Measurements were made (a) with the Aerobika* OPEP device inserted between the BAN and induction port, and (b) substituting the acapella® duet OPEP device. The BAN was run to sputter, and the therapeutically beneficial fine particle mass FMipr ) determined. Results FMipr (mean±SD) via the BAN alone, with the BAN-Aerobika*, and the BAN-acapella® duet OPEP devices were 452±28, 426±27 and 308±23 mg respectively. The BAN-Aerobika* combination marginally reduced delivery (paired t-test, p=0.043), whereas the BAN-acapella® duet configuration resulted in substantial losses (p Conclusion An AeroEclipse®-II BAN-Aerobika* OPEP combination offers combined aerosol/OPEP therapy with minimal medication loss. Substitution with the acapella® duet OPEP results in substantial reduction in BAN-output that may have adverse clinical implications.

Deposition of Particles in Human Mouth-Throat Replicas and a USP Induction Port.

Oral inhalation is the common route of drug delivery to pulmonary airways. In general, deposition in the oropharyngeal airways from a drug-delivery device makes up a substantial portion of the emitted dose, which affects the dose delivered to the lung. Studies with airway replicas made from cadaver or magnetic resonance imaging scans show that for micrometer-sized particles, impaction is the dominant deposition mechanism. Several deposition studies in oropharyngeal replicas found that the deposition efficiency can be correlated with the mouth inlet velocity and inlet mouthpiece diameter. Other studies show that the deposition efficiency is best correlated with the mean diameter of internal geometry and the mean velocity based on the mean diameter. We investigated the mouth inlet diameter, as well as internal airway dimensions and their influence on oropharyngeal deposition based on experimental data from this study. Several human oropharyngeal replicas with different mouth inlet diameters and the USP induction port were used. We found that the aerosol deposition increased with decreasing mouth inlet diameter. Several mathematical expressions were tried to correlate the deposition efficiency with the Stokes number calculated based on (1) mouth inlet diameter and inlet velocity, (2) mean diameter of internal geometry and mean velocity, (3) mouth inlet velocity and mean diameter, and (4) mouth inlet velocity and minimum diameter in the oropharyngeal replica. The best correlation was obtained in case 4. This correlation could explain the intra-subject variation when deposition was found to vary with mouth inlet diameter, such as in some aerosol drug-delivery devices. It could also explain the intersubject variability in oropharyngeal deposition when human volunteers with different airway geometries and mouth openings were studied.

Performance of Dry Powder Inhalers with Single Dosed Capsules in Preschool Children and Adults Using Improved Upper Airway Models

The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction port according to the European Pharmacopeia were used for in vitro testing of dry powder inhalers with single dosed capsules (Cyclohaler®, Handihaler® and Spinhaler®). Deposition measurements were performed using steady flow rates of 30 and 60 L/min for the Handihaler®/Spinhaler® and 30, 60 and 75 L/min for the Cyclohaler®. The inhalation volume was set at 1 L. For the Cyclohaler®, the in vitro testing was supplemented by a pediatric inhalation profile. Slight differences of pulmonary deposition between the idealized adult (11%–15%) and pediatric (9%–11%) upper airway model were observed for the Cyclohaler®. The applied pediatric inhalation profile resulted in a reduction of pulmonary deposition by 5% compared to steady conditions and indicated the influence of the inhalation pattern on the amount of pulmonary deposited particles. The comparison of two pediatric upper airway models showed no differences. The performance of the Handihaler® was similar to the Cyclohaler®. The Spinhaler® showed an insufficient performance and limited reproducibility in our investigations.

The solid-state and morphological characteristics of particles generated from solution-based metered dose inhalers: Influence of ethanol concentration and intrinsic drug properties

The aerosol performance, physical properties and formation process of two corticosteroids (beclomethasone dipropionate and fluticasone propionate) and caffeine (active pharmaceutical ingredients: APIs) from ethanol-based pressurized metered dose inhaler solution formulations, containing various ethanol fractions, were evaluated using cascade impaction, thermal analysis and scanning electron microscopy. In general, the final aerosol particle size distribution (post USP induction port) was unaffected by ethanol concentration (mass median aerodynamic diameter and geometric standard deviation values for each formulation were independent of ethanol concentration (%, w/w) in the initial formulation). However, ethanol concentration directly affected the percentage of particles that passed the USP induction, resulting in a significant decrease in fine particle fraction, across all formulations, as ethanol was increased. Thus it can be concluded that particle size is governed by initial droplet diameter and API concentration, while performance is governed by drying time. The physico-chemical properties and morphology of the dried API particles, collected from cascade impactor stages, showed that the solid state was related to the glass transition temperature (Tg) and, to some extent, the saturated hydrofluoroalkane propellant (HFA)/ethanol solubility of the APIs. The low Tg API caffeine, with high HFA solubility resulted in crystalline particles, while the high Tg corticosteroids were amorphous. Furthermore, the final structure of the particles was dependent on the ethanol concentration and drying kinetics after initial droplet formation. This study has shown that the solid-state physico-chemical properties and morphology of particles is intrinsically linked to the API properties and drying kinetics of the propellant/co-solvent. These variations in aerosol efficiency, particle morphology and solid-state characteristics may have direct effects on drug efficacy and bioavailability after deposition in the lung.

Potential of a Cyclone Prototype Spacer to Improve In Vitro Dry Powder Delivery

PurposeLow inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrier-based DPIs was investigated.MethodsCyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30 and 60 Lmin−1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography.ResultsReduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51% at 30 Lmin−1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 μm vs. 3.00 ± 0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates.ConclusionThis work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.

Effect of Device Design on the Aerosolization of a Carrier-Based Dry Powder Inhaler—a Case Study on Aerolizer® Foradile®

The objective of this study is to investigate the effect of device design of the Aerolizer(®) on the aerosolization of a carrier-based dry powder inhaler formulation (Foradile(®)). The Aerolizer was modified by reducing the air inlet size and mouthpiece length to 1/3 of the original dimensions, or by increasing the grid voidage. Aerosolization of the powder formulation was assessed on a multi-stage liquid impinger at air flow rates of 30, 60, and 100 L/min. Coupled CFD-DEM simulations were performed to investigate the air flow pattern and particle impaction. There was no significant difference in the aerosolization behavior between the original and 1/3 mouthpiece length devices. Significant increases in FPF total and FPF emitted were demonstrated when the inlet size was reduced, and the results were explained by the increases in air velocity and turbulence from the CFD analysis. No significant differences were shown in FPF total and FPF emitted when the grid voidage was increased, but more drugs were found to deposit in induction port and to a lesser extent, the mouthpiece. This was supported by the CFD-DEM analysis which showed the particle-device collisions mainly occurred in the inhaler chamber, and the cross-grid design increased the particle-device collisions on both mouthpiece and induction port. The air inlet size and grid structure of the Aerolizer(®) were found to impact significantly on the aerosolization of the carrier-based powder.

Good Cascade Impactor Practice (GCIP) and Considerations for “In-Use” Specifications

The multi-stage cascade impactor (CI) is widely used to determine aerodynamic particle size distributions (APSDs) of orally inhaled products. Its size-fractionating capability depends primarily on the size of nozzles of each stage. Good Cascade Impactor Practice (GCIP) requires that these critical dimensions are linked to the accuracy of the APSD measurement based on the aerodynamic diameter size scale. Effective diameter (Deff) is the critical dimension describing any nozzle array, as it is directly related to stage cut-point size (d50). d50 can in turn be determined by calibration using particles of known aerodynamic diameter, providing traceability to the international length standard. Movements in Deff within manufacturer tolerances for compendial CIs result in the worst case in shifts in d50 of <±10%. Stage mensuration therefore provides satisfactory control of measurement accuracy. The accurate relationship of Deff to d50 requires the CI system to be leak-free, which can be checked by sealing the apparatus at the entry to the induction port and isolating it from the vacuum source and measuring the rate of pressure rise before each use. Mensuration takes place on an infrequent basis compared with the typical interval between individual APSD determinations. Measurement of stage flow resistance (pressure drop; ΔPstage) could enable the user to know that the CI stages are fit for use before every APSD measurement, by yielding an accurate measure of Deff. However, more data are needed to assess the effects of wear and blockage before this approach can be advocated as part of GCIP.

Quantitative Analysis and Design of a Spray Aerosol Inhaler. Part 2: Improvements in Mouthpiece Performance

The objective of this study was to utilize previously identified critical design attributes for the capillary aerosol generator as a model spray inhaler in order to develop a second-generation device that minimized aerosol drug deposition in the mouthpiece. Computational fluid dynamics (CFD) predictive analysis of the critical design attributes indicated that turbulence intensity should be reduced and the effective mouthpiece diameter should be increased. Two second-generation inhaler mouthpieces meeting these specifications were manufactured and tested. The first device (Design 1) implemented a larger cross-sectional area in the mouthpiece and streamlined flow, whereas the second device (Design 2) used a perforated mouthpiece wall. An in vitro deposition study was performed to quantify the deposition of drug mass in the mouthpieces and connected induction ports, and the results were compared with the CFD predictions. The two second-generation mouthpieces reduced in vitro aerosol deposition from the original value of 7.8% to values of 2.1% (Device 1) and 4.3% (Device 2), without largely altering the induction port deposition. This was achieved by design alterations aimed at reducing turbulence intensity and increasing the effective mouthpiece diameter. CFD model predictions were in good agreement with the in vitro experimental data. A second-generation spray inhaler mouthpiece with low drug deposition was developed using a predictive CFD model and in vitro experiments. Applying this quantitative analysis and design methodology to medical devices, which is similar to the Quality by Design paradigm, could provide significant advantages compared with traditional approaches.

Adapting the Abbreviated Impactor Measurement (AIM) Concept to Make Appropriate Inhaler Aerosol Measurements to Compare with Clinical Data: A Scoping Study with the “Alberta” Idealized Throat (AIT) Inlet

The Abbreviated Impactor Measurement (AIM) concept simplifies determination of aerodynamic size metrics for inhaler quality control testing. A similar approach is needed to compare in vitro particle size distribution metrics with human respiratory tract (HRT) deposition. An abbreviated impactor based on the Andersen eight-stage cascade impactor (ACI) was developed having two size-fractionating stages with cut-points at 4.7 and 1.1 μm aerodynamic diameter at 28.3 L/min, to distinguish between coarse (CPM), fine (FPM), and extra-fine (EPM) mass fractions likely to deposit in the oropharynx, airways of the lungs, or be exhaled, respectively. In vitro data were determined for pressurized metered dose inhaler (pMDI)-delivered salbutamol (100 μg/actuation ex valve) with an "Alberta" idealized adult upper airway (throat) inlet (AIM-pHRT). Corresponding benchmark data for a full resolution Andersen eight-stage cascade impactor with "Alberta" idealized throat (ACI-AIT) and ACI-Ph.Eur./USP inlet were obtained with the same product. Mass recoveries (μg/actuation; mean ± SD) were equivalent at 100.5 ± 0.7; 97.2 ± 4.9 and 101.5 ± 9.5 for the AIM-pHRT, ACI-AIT, and ACI-Ph.Eur./USP induction port, respectively [one-way analysis of variance (ANOVA), p=0.64]. Corresponding values of CPM were 59.2 ± 4.2; 58.4 ± 2.4, and 65.6 ± 5.8; the AIT captured larger particles more efficiently than the Ph.Eur./USP induction port, so that less large particle mass was apparent in the upper stages of the ACI-AIT (p ≤ 0.037). Equivalent values of FPM were similar regardless of inlet/abbreviation at 41.3 ± 4.2; 38.7 ± 3.0, and 35.9 ± 3.8 (p=0.054), and EPM measures (1.7 ± 0.3; 2.0 ± 0.5; 2.1 ± 0.3) were also comparable (p=0.32). The AIT inlet significantly increased the capture of the coarse fraction compared with that collected by the Ph.Eur./USP induction port. Measures obtained using the AIM-pHRT apparatus were comparable with those obtained with the ACI-AIT.

Effect of Sampling Volume on Dry Powder Inhaler (DPI)-Emitted Aerosol Aerodynamic Particle Size Distributions (APSDs) Measured by the Next-Generation Pharmaceutical Impactor (NGI) and the Andersen Eight-Stage Cascade Impactor (ACI)

Current pharmacopeial methods for testing dry powder inhalers (DPIs) require that 4.0 L be drawn through the inhaler to quantify aerodynamic particle size distribution of "inhaled" particles. This volume comfortably exceeds the internal dead volume of the Andersen eight-stage cascade impactor (ACI) and Next Generation pharmaceutical Impactor (NGI) as designated multistage cascade impactors. Two DPIs, the second (DPI-B) having similar resistance than the first (DPI-A) were used to evaluate ACI and NGI performance at 60 L/min following the methodology described in the European and United States Pharmacopeias. At sampling times ≥2 s (equivalent to volumes ≥2.0 L), both impactors provided consistent measures of therapeutically important fine particle mass (FPM) from both DPIs, independent of sample duration. At shorter sample times, FPM decreased substantially with the NGI, indicative of incomplete aerosol bolus transfer through the system whose dead space was 2.025 L. However, the ACI provided consistent measures of both variables across the range of sampled volumes evaluated, even when this volume was less than 50% of its internal dead space of 1.155 L. Such behavior may be indicative of maldistribution of the flow profile from the relatively narrow exit of the induction port to the uppermost stage of the impactor at start-up. An explanation of the ACI anomalous behavior from first principles requires resolution of the rapidly changing unsteady flow and pressure conditions at start up, and is the subject of ongoing research by the European Pharmaceutical Aerosol Group. Meanwhile, these experimental findings are provided to advocate a prudent approach by retaining the current pharmacopeial methodology.

Does the United States Pharmacopeia Throat Introduce De-agglomeration of Carrier-Free Powder from Inhalers?

We hypothesize that the USP induction port may de-agglomerate carrier-free powder emitting from dry powder inhalers (DPIs). Aerosols emitting from a range of DPIs (Spinhaler®, Turbuhaler® and Osmohaler™) and induction ports (USP throat, straight tube, Alberta idealized mouth-throat geometry (AG)) were sized by laser diffraction. Total drug recovery was obtained by HPLC and fine particle fraction computed. Air flow patterns were simulated using Computational Fluid Dynamics (CFD). The straight tube did not de-agglomerate emitted powder. However, the USP throat and AG further de-agglomerated powders from the Spinhaler, but not the Turbuhaler and Osmohaler. While budesonide powder deposited similarly in all induction ports, deposition was significantly higher in the AG for both DSCG and mannitol. CFD revealed agglomerates impacting on the USP throat with higher localized velocity compared with the straight tube. CFD further showed a more complex flow pattern with high-velocity air jets in the AG, which explains the higher FPF for DSCG and the lower FPF for mannitol using the AG. The USP throat further de-agglomerated the emitted powder from the DPI when it did not sufficiently disperse the powder. Other tools such as laser diffraction may be used for cross-examining to avoid artifacts in the results.

Comparison of Deposition in the USP and Physical Mouth–Throat Models with Solid and Liquid Particles

Experimental deposition was studied using three different mouth-throat models: (1) the standard United States Pharmacopeia induction port (IP), (2) the idealized human mouth and throat replica developed by the University of Alberta (UofA replica), and (3) the conductive rubber mouth-throat cast from a human subject developed by Lovelace Respiratory Research Institute (LRRI cast). Both solid and liquid monodispersed fluorescent particles in the size range of 2-30 μm in diameter were delivered into the devices at flow rates of 15, 30, and 60 L min(-1). For solid particles, the study was conducted with and without grease coating inside the devices to investigate the effects of particle bounce. Large amounts of rebounded particles were found for the IP and UofA replica without the coating treatment, while particle bounce was only observed at the large particle size for the LRRI cast. The UofA replica and LRRI cast agreed well for solid particles with coating treatments and liquid particles. The deposition results from this study were also compared to data of in vivo deposition studies from the literature. The deposition efficiencies in the UofA replica and LRRI cast were within the range of in vivo data, which showed a large scatter.

The Interaction Between the Oropharyngeal Geometry and Aerosols via Pressurised Metered Dose Inhalers

This study investigated the effect of oropharyngeal geometry on inhaled aerosol characteristics via pressurised metered dose inhalers (pMDIs), both with or without spacers. Seven adult oropharyngeal models with different centreline lengths, total volumes, and degrees of constriction were employed as induction ports for a laser diffraction particle size analyser and cascade impactor. Particle size change over time, mass median aerodynamic diameter (MMAD), average median volume diameter (D(V)50), inhaled doses, and oropharyngeal depositions (percentage of the nominal dose) for aerosols via suspension and ultrafine pMDIs with or without spacers at 30 l/min airflow were determined. Variations in oropharyngeal geometry caused significant variations in inhaled particle size distributions, doses, oropharyngeal drug depositions, and particle size change over time when pMDIs were used without spacers. However, inhaled aerosol characteristics had marginal variations for the ultrafine pMDI plus large volume spacer (MMAD range: 0.69-0.78 microm, D(V)50 range: 1.27-1.36 microm, inhaled dose range: 46.46-52.92%). It was found that the amounts of inhaled aerosol particles with aerodynamic size of less than 0.83 microm via pMDIs plus large volume spacer were slightly affected by the oropharyngeal geometry. Inhaling ultrafine aerosols via spacers may reduce the effect of oropharyngeal geometry on inhaled aerosol properties.

Quantitative Analysis and Design of a Spray Aerosol Inhaler. Part 1: Effects of Dilution Air Inlets and Flow Paths

The objective of this study was to evaluate the effects of modifying inhaler design variables on aerosol drug deposition within the mouthpiece for a representative spray system using a quantitative analysis and design approach. Capillary aerosol generation (CAG) was selected as a model spray aerosol system in conjunction with four prototype inhaler body and mouthpiece combinations. In vitro experiments were used to determine drug deposition in the mouthpiece and induction port. Validated computational fluid dynamics (CFD) simulations were implemented to establish relationships between design variables, transport characteristics, and aerosol drug deposition. Results of this study indicated that both the size of the upstream dilution air inlets and the flow pathway configuration near the spray nozzle significantly influenced aerosol transport and deposition. CFD results showed that the primary transport characteristics associated with drug deposition were turbulence intensity and the effective diameter of the mouthpiece. Strong quantitative correlations were developed between the identified transport characteristics and mouthpiece drug deposition. Based on quantitative analysis and design, turbulence intensity and effective mouthpiece diameter were identified as key transport characteristics within the design space that directly influenced aerosol deposition and may be used to predict and optimize drug delivery to the patient.