Mean Mass Median Aerodynamic Diameter Research Articles

Comparison of HPMC Inhalation-Grade Capsules and Their Effect on Aerosol Performance Using Budesonide and Rifampicin DPI Formulations.

Despite the fact that capsules play an important role in many dry powder inhalation (DPI) systems, few studies have been conducted to investigate the capsules’ interactions with respirable powders. The effect of four commercially available hydroxypropyl methylcellulose (HPMC)inhalation-grade capsule types on the aerosol performance of two model DPI formulations (lactose carrier and a carrier-free formulation) at two different pressure drops was investigated in this study. There were no statistically significant differences in performance between capsules by using the carrier-based formulation. However, there were some differences between the capsules used for the carrier-free rifampicin formulation. At 2-kPa pressure drop conditions, Embocaps® VG capsules had a higher mean emitted fraction (EF) (89.86%) and a lower mean mass median aerodynamic diameter (MMAD) (4.19 µm) than Vcaps® (Capsugel) (85.54%, 5.10 µm) and Quali-V® I (Qualicaps) (85.01%, 5.09 µm), but no significant performance differences between Embocaps® and ACGcaps™ HI. Moreover, Embocaps® VG capsules exhibited a higher mean respirable fraction (RF)/fine particle fraction (FPF) with a 3-µm–sized cutoff (RF/FPF< 3 µm) (33.05%/35.36%) against Quali-V® I (28.16%/31.75%) (P < 0.05), and a higher RF/FPF with a 5-µm–sized cutoff (RF/FPF< 5 µm) (49.15%/52.57%) versus ACGcaps™ HI (38.88%/41.99%) (P < 0.01) at 4-kPa pressure drop condition. Aerosol performance variability, pierced-flap detachment, as well as capsule hardness and stiffness, may all influence capsule type selection in a carrier-based formulation. The capsule type influenced EF, RF, FPF, and MMAD in the carrier-free formulation.

Droplet Size and Distribution of Nebulized 3% Sodium Chloride, Albuterol, and Epoprostenol by Phase Doppler Particle Analyzer

BackgroundAerosolized drug therapy administered to mechanically ventilated patients is a standard part of pulmonary critical care medicine. Aerosol particle size and distribution are important factors in the optimal delivery of aerosolized drugs to ventilated patients.ObjectiveThe objective of this study was to characterize aerosol droplet size and distribution with laser diffraction for nebulized 3% sodium chloride, albuterol, and epoprostenol sodium (containing glycine) delivered via Aeroneb Solo Mesh Nebulizers (Aerogen, Mountain View, California).MethodsA series of functional flow tests were run on each of 8 Solo mesh nebulizers before the study to verify accuracy of flow rates in milliliters per minute. Aerosolized droplets exiting the nebulizer heads were then measured using a phase Doppler particle analyzer. Data collected during delivery of 3% sodium chloride, albuterol, and epoprostenol sodium included aerosol droplet size distribution, mass median aerodynamic diameter (MMAD), and geometric standard deviation. For each Solo nebulizer, droplet size measurements were taken 2 cm away from the nebulizer head and 2 cm away from the wye of a heated, humidified adult ventilator circuit. For measurements taken at the wye, 4 distinct, continuous flow rates (2, 10, 20, and 40 L/min) were generated by an air pump to simulate inspiratory flows delivered with mechanical ventilation. The expiratory limb was capped, and the nebulizer head was inserted into the breathing circuit upstream of the humidifier.ResultsEach Solo nebulizer met Aerogen's recommended minimum flow rate of 0.2 mL/min, ranging from 0.23 to 0.31 mL/min. The MMAD of the 3 tested aerosols was several times smaller when measured at the wye outlet of the heated/humidified breathing circuit (0.82–2.73 µm) compared with droplets measured directly at the nebulizer outlet (MMAD, 4.6–7.3 µm). There was also significant variability across Solo heads with some ventilator flow rates. The mean MMAD at the wye for the 3% sodium chloride solution, albuterol, and epoprostenol test solutions was 1.62 µm, 1.09 µm, and 1.18 µm, respectively. The mean MMAD at the nebulizer for the 3% sodium chloride solution, albuterol, and epoprostenol test solutions was 5.37 µm, 5.73 µm, and 6.73 µm, respectively.ConclusionsResults from this study suggest that particle size of aerosolized drugs administered via a commonly used setup for delivery of in-line aerosols to mechanically ventilated patients may be several times smaller than expected and may result in less drug being delivered to the patient than previously realized.(Curr Ther Res Clin Exp. 2021; 82:XXX–XXX)© 2021 Elsevier HS Journals, Inc.

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

Background: 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. Methods: An inline DPI was developed that consisted of hollow inlet and outlet capillaries, a powder chamber, and a nasal or oral interface. A ventilation bag or compressed air was used to actuate the device and simultaneously provide a full deep inspiration consistent with a 5-year-old child. The powder chamber was partially filled with a model spray-dried excipient enhanced growth powder formulation with a mass of 10 mg. Device aerosolization was characterized with cascade impaction, and aerosol transmissions through oral and nasal in vitro models were assessed. Results: Best device performance was achieved when all actuation air passed through the powder chamber (no bypass flow) resulting in an aerosol mean mass median aerodynamic diameter (MMAD) <1.75 μm and a fine particle fraction (<5 μm) ≥90% based on emitted dose. Actuation with the ventilation bag enabled lung delivery efficiency through the nasal and oral interfaces to a tracheal filter of 60% or greater, based on loaded dose. In both oral and nose-to-lung (N2L) administrations, extrathoracic depositional losses were <10%. Conclusion: In conclusion, this study has proposed and initially developed an efficient inline DPI for delivering spray-dried formulations to children using positive pressure operation. Actuation of the device with positive pressure enabled effective N2L aerosol administration with a DPI, which may be beneficial for subjects who are too young to use a mouthpiece or to simultaneously treat the nasal and lung airways of older children.

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

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. 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 10ml air bursts. CFD simulations of device operation were used to predict flow field and particle-based dispersion parameters. 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 = 0.04μm) 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. A unique relationship was identified in the DAC-unit DPI in which reducing turbulence also reduced the MMAD.

In Vitro Characterization of the eFlow Closed System Nebulizer with Glycopyrrolate Inhalation Solution.

Background: Glycopyrrolate administered by a novel, investigational eFlow® Closed System (CS) nebulizer (eFlow CS) is being evaluated for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The eFlow CS is a hand-held, vibrating membrane nebulizer optimized to deliver 1 mL of glycopyrrolate solution into the lung in <3 minutes. Clinical studies have shown improvements in lung function of subjects treated with nebulized glycopyrrolate.Methods: The aerosol performance of the eFlow CS nebulizer was characterized by delivered dose, aerodynamic droplet size distribution and nebulization time. Simulated use nebulizer performance over 60 days was assessed by volume median diameter (VMD), nebulized amount, and nebulization time. Nebulization outputs were assayed to ensure adequate delivery of glycopyrrolate with an acceptable impurity profile. Aerosol condensates were analyzed for glycopyrrolate concentration and impurities by ultra-high-performance liquid chromatography and compared with non-nebulized samples.Results: The mean mass median aerodynamic diameter, geometric standard deviation, and fine particle fraction were 3.7 μm, 1.7, and 72%, respectively, and independent of formulation strength (25 and 50 μg/mL). Delivered dose was 88% of the nominal dose for both formulation strengths. The mean delivered dose, assessed by breathing simulation, was 56.8% for 25 μg/mL and 62.6% for 50 μg/mL. Nebulization times were 1–2.5 minutes with no apparent increasing trend with use over a 60-day period. The nebulized amount showed no significant changes, whereas the VMD showed a slight, but not pharmaceutically relevant, increase (0.1–0.2 μm) after 60-day simulated use. Glycopyrrolate concentration and impurity levels of nebulized samples were statistically similar to those of non-nebulized samples.Conclusion: The eFlow CS generates glycopyrrolate aerosols with high delivered dose, short treatment time, and small droplet size with narrow size distribution suitable for central and peripheral airway deposition. The unit dose vial mitigates medication misuse and ensures dose uniformity. Results support the use of glycopyrrolate/eFlow CS for the treatment of COPD.

Development of an Inline Dry Powder Inhaler That Requires Low Air Volume.

Inline dry powder inhalers (DPIs) are actuated by an external air source and have distinct advantages for delivering aerosols to infants and children, and to individuals with compromised lung function or who require ventilator support. However, current inline DPIs either perform poorly, are difficult to operate, and/or require large volumes (∼1 L) of air. The objective of this study was to develop and characterize a new inline DPI for aerosolizing spray-dried formulations with powder masses of 10 mg and higher using a dispersion air volume of 10 mL per actuation that is easy to load (capsule-based) and operate. Primary features of the new low air volume (LV) DPIs are fixed hollow capillaries that both pierce the capsule and provide a continuous flow path for air and aerosol passing through the device. Two different configurations were evaluated, which were a straight-through (ST) device, with the inlet and outlet capillaries on opposite ends of the capsule, and a single-sided (SS) device, with both the inlet and outlet capillaries on the same side of the capsule. The devices were operated with five actuations of a 10 mL air syringe using an albuterol sulfate (AS) excipient-enhanced growth (EEG) formulation. Device emptying and aerosol characteristics were evaluated for multiple device outlet configurations. Each device had specific advantages. The best case ST device produced the smallest aerosol [mean mass median aerodynamic diameter (MMAD) = 1.57 μm; fine particle fraction <5 μm (FPF<5μm) = 95.2%)] but the mean emitted dose (ED) was 61.9%. The best case SS device improved ED (84.8%), but produced a larger aerosol (MMAD = 2.13 μm; FPF<5μm = 89.3%) that was marginally higher than the initial deaggregation target. The new LV-DPIs produced an acceptable high-quality aerosol with only 10 mL of dispersion air per actuation and were easy to load and operate. This performance should enable application in high and low flow mechanical ventilation systems and high efficiency lung delivery to both infants and children.

Nebulizer Delivery of Micafungin Aerosols

To determine the optimal nebulization system for aerosolizing micafungin and to further assess the physiochemical properties of aerosolized micafungin. In vitro experiment. University research center. NEBULIZERS: Pari LC Star, Hudson Updraft, Small Volume Nebulizer, and Aeroclipse II. Using a commercially available cascade impactor, the four nebulizers were tested for their ability to deliver micafungin to the lungs. Mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) percent less than 3.3 μm (FPF(3.3)) and less than 5.8 μm (FPF(5.8)) were determined during two sampling periods for each of three trials of all nebulizers. The mean ± standard error of the mean MMAD for the nebulizers ranged from 1.93 ± 0.09 to 2.49 ± 0.25 μm; FPF(3.3) and FPF(5.8) were approximately 50% and 90%, respectively, for all nebulizers. Although all nebulizers appeared acceptable to deliver micafungin to the lungs, the Pari LC Star had the smallest MMAD and highest FPF(3.3) and FPF(5.8). These properties of the Pari LC Star should result in greater delivery of the aerosol to the lungs. Additional research on pulmonary delivery and clinical tolerability is warranted.

Size distribution of airborne particulate matter and associated heavy metals in the roadside environment

The size distributions of airborne particulate matter (PM) and associated heavy metals Pb, Cd, Ni, Cr, V, Mn, Cu and Fe in different inhalable fractions (<0.8 μm, 0.8–1.3 μm, 1.3–2.7 μm, 2.7–6.7 μm and >6.7 μm) were determined at a traffic-orientated urban site in the city of Thessaloniki, northern Greece. The airborne PM displayed a bimodal distribution with most of the mass (52%) contained in the submicron size range (<0.8 μm) and an additional minor mode (20%) in the coarse size fraction (>6.7 μm). Characteristic size distributions of heavy metals allowed identification of three main behavioral types: (a) metals whose mass was resided mainly within the accumulation mode (Pb, Cd), (b) those which were distributed between fine, intermediate and coarse modes (Ni, Cu, Mn), and (c) those which were mainly found within particles larger than 2.7 μm in diameter (Fe). The mean mass median aerodynamic diameter (MMAD) of PM was found at 0.85 ± 0.71 μm, while the mean MMADs of heavy metals followed the order Pb (0.96 ± 0.71 μm) < Cd (1.14 ± 0.82 μm) < V (1.38 ± 0.63 μm) < Ni (1.45 ± 0.88 μm) < Cu (2.04 ± 0.77 μm) < Mn (2.61 ± 1.23 μm) < Cr (2.91 ± 1.40 μm) < Fe (3.82 ± 0.88 μm). The measured distributions are believed to result from a combination of processes including local anthropogenic and natural sources, such as traffic, industrial emissions and resuspension of road dust.

Size Distribution of Chromate Paint Aerosol Generated in a Bench-Scale Spray Booth

Spray painters are potentially exposed to aerosols containing hexavalent chromium [Cr(VI)] via inhalation of chromate-based paint sprays. Evaluating the particle size distribution of a paint spray aerosol, and the variables that may affect this distribution, is necessary to determine the site and degree of respiratory deposition and the damage that may result from inhaled Cr(VI)-containing paint particles. This study examined the effect of spray gun atomization pressure, aerosol generation source and aerosol aging on the size distribution of chromate-based paint overspray aerosols generated in a bench-scale paint spray booth. The study also determined the effect of particle bounce inside a Marple personal cascade impactor on measured size distributions of paint spray aerosols. Marple personal cascade impactors with a modified inlet were used for sample collection. The data indicated that paint particle bounce did not occur inside the cascade impactors sufficiently to affect size distribution when using uncoated stainless steel or PVC substrate sampling media. A decrease in paint aerosol mass median aerodynamic diameter (MMAD) from 8.2 to 7.0 mum was observed as gun atomization pressure increased from 6 to 10 psi. Overspray aerosols were sampled at two locations in the spray booth. A downstream sampling position simulated the exposure of a worker standing between the painted surface and exhaust, a situation encountered in booths with multiple workers. The measured mean MMAD was 7.2 mum. The distance between the painted surface and sampler was varied to sample oversprays of varying ages between 2.8 and 7.7 s. Age was not a significant factor for determining MMAD. Overspray was sampled at a 90 degrees position to simulate a worker standing in front of the surface being painted with air flowing to the worker's side, a common situation in field applications. The resulting overspray MMAD averaged 5.9 mum. Direct-spray aerosols were sampled at ages from 5.3 to 11.7 s. Overspray and direct-spray results indicated that most of the change in aerosol size distribution occurred between the time the paint aerosol impacted the painted surface and the time the overspray became 2.8 s old. The overall mean MMAD of overspray in the study was 6.4 mum and may have been underestimated due to sampling efficiency biases. If inhaled by a worker, the overspray aerosols evaluated in this study would mostly deposit in the head airways region of the respiratory tract. Paint overspray aerosols contained Cr primarily in the Cr(VI) state.

Gas/particle partitioning and size distribution of primary and secondary carbonaceous aerosols in public buildings.

The gas and particulate phase of semi-volatile organic compounds (six samples) and the composition of organic aerosol as a function of particle size (six samples) were studied in two public buildings in Greece. The objectives of this study were: i) to chemically characterize the organic content of indoor gas and particulate phases; ii) to classify indoor organic aerosol constituents as a function of particle size; and iii) to reconcile the sources of organic compounds indoors. Non-polar, semi-polar, polar, and acidic compounds were identified in both gas and particulate phases by using gas chromatography/mass spectrometry (GC/MS). Branched iso- and anteiso-alkanes were used to trace environmental tobacco smoke (ETS) concurrently with other compounds. Polycyclic aromatic hydrocarbons (PAHs) in the gas phase gave a pattern more characteristic to ETS than the corresponding pattern in the particulate phase. The chemical composition observed for n-alkanols and n-alkanoic acids in both gas and particulate phases indicated ETS as one of their main sources indoors. PAHs and n-alkanols were evenly associated between fine and coarse particles and their corresponding total mean mass median aerodynamic diameter (MMAD) was 1.27 and 1.38 microns respectively, indicating a mixed origin. Conversely, the MMAD of n-alkanes, unresolved complex mixture (UCM), iso- and anteiso-alkanes and free fatty acids varied from 0.30 to 0.62 micron denoting a stronger association with indoor sources.

Characterization of 99mTc-DTPA Aerosols for Lung Permeability Studies

Background: The interpretation of ^99mTc diethylenetriamine pentaacetate (^99mTc DTPA) aerosol clearance is based on the hypothesis that the ^99mTc-DTPA complex is not altered by the nebulization process. Objectives: To characterize (1) the radiochemical purity (RCP) of ^99mTc-DTPA and the stability of labeling after jet nebulization, and (2) the particle size distribution of the aerosol. Methods: RCP and stability – the aerosol was driven by oxygen, captured on filters which were eluted and RCP was checked by thin layer chromatography. Particle size distribution – the aerosol was generated using dry air (50 psi) at three different flow rates, i.e. 3 (1 run), 6 (4 runs) and 9 l·min^–1 (4 runs). The mass median aerodynamic diameter (MMAD) and the geometric standard deviation (σg) were determined using a cascade impactor from the radioactivity counted on each stage. Results: The RCP was more than 95% in all cases. Mean MMAD (±SD) was 0.70 µm (±0.07) at 9 l·min^–1, 0.93 µm (±0.05) at 6 l·min^–1 (p < 0.05) and 1.50 µm at 3 l·min^–1. Mean σg (±SD) was 2.02 (±0.08) at 9 l·min^–1, 2.00 (±0.16) at 6 l·min^–1 and 1.90 at 3 l·min^–1. Conclusion: This study demonstrates (1) that the high RCP of ^99mTc-DTPA is not affected by jet nebulization, even when using oxygen at a high flow rate, and (2) that when using a flow rate between 6 and 9 l·min^–1, the MMAD remains optimal for peripheral lung deposition.