Airborne emissions and corrosion of stainless bellows under simulated semiconductor halide environment.

High dose dry powder inhalation of itraconazole nanocrystals: Impact of drug load and inhalation device.

Device actuation was performed following 0 to 5 pre-actuation shakes. Performance was assessed using a multi-technique approach: cascade impaction, dose uniformity testing (DUSA), laser diffraction (SprayTec), optical microscopy, and scanning electron microscopy (SEM). Key parameters measured included emitted dose (ED), delivered dose (DD), fine particle dose (FPD), fine particle fraction (FPF), mass median aerodynamic diameter (MMAD), and throat deposition. Delivered dose remained relatively constant regardless of shaking. However, FPD and FPF significantly improved with increased shaking, particularly at three to five shakes. Cascade impaction demonstrated reduced throat deposition and greater deposition in stages 3-4 (< 5µm respirable fraction) under these conditions. An inverse correlation between throat deposition and FPF was identified. SEM and microscopy confirmed consistent particle morphology and blend uniformity, while laser diffraction showed a predominance of larger carrier particles under 0-shake conditions. Pre-actuation shaking substantially influences the aerosolization performance of Easyhaler® Salbutamol. At least three vertical shakes are required to achieve optimal fine particle delivery and reduce throat deposition. These findings highlight the importance of proper patient instruction on device handling. Further studies should assess whether similar effects occur with other Easyhaler® formulations.

Ciprofloxacin (CFX)is a potent antibiotic for respiratory infections,but its poor solubility and high crystallinity limit its effectivenessin dry powder inhaler (DPI) delivery. Although soluble forms suchas CFX hydrochloride are available, their rapid dissolution may leadto systemic absorption, undermining localized lung targeting. To addressthis, we developed solid dispersions of CFX with primary bile acids,namely, cholic acid (CA) and chenodeoxycholic acid (CDA), using spraydrying and ball milling to enhance solubility in a controlled mannerwhile maintaining deposition in the lungs. Differential scanning calorimetryshowed glass-transition temperature (Tg) values were elevated for both bile acids, with CA dispersions showingslightly higher absolute values (114.16–131.77 °C vs 109.13–120.67°C). However, Fourier transform infrared and dissolution dataindicated that CDA formed stronger directional hydrogen bonding withCFX. X-ray diffraction confirmed partially amorphous dispersions withminimal residual crystallinity. Solubility enhancement was observedfor both bile acids, showing slightly higher values with CA dispersions.Aerodynamic assessments using an Andersen cascade impactor revealedimproved lung deposition with CFX–CDA, with a higher fine particlefraction (FPF: 30.81%) and lower mass median aerodynamic diameter(MMAD: 5.89 μm) compared to CFX–CA (FPF: 26.93%, MMAD:6.19 μm). The emitted dose was highest in CDA with nearly 5mg compared to CA dispersions (∼3 mg). In vitro antimicrobialstudies showed that dispersions maintained comparable antimicrobialactivity to pure CFX, while in vivo toxicology in rats indicated mild,dose-dependent hepatic changes. CDA formulations showed AST elevationat a low dose and ALP increase at a high dose, consistent with theknown hepatic effects of this bile acid, while CA formulations werebroadly comparable to pure CFX. Machine learning algorithms, includingtree-based models and neural networks, were used to predict the formulationperformance and identify critical variables. Feature selection wasachieved using recursive elimination, and permutation analysis showedthat the bile acid type, inlet temperature, and molar ratio were themost influential predictors of solubility and lung deposition. Modelssuch as gradient boosting and elastic net showed a high predictiveaccuracy (R2 > 0.85). Overall, thisstudyhighlights the potential of primary bile acid-based DPI formulationsas effective inhalable antibiotic therapies.

Crizotinib is a targeted therapy for metastatic non-small cell lung cancer (NSCLC) that is ALK- or ROS1-positive, as well as for conditions such as ALK-positive anaplastic large cell lymphoma and inflammatory myofibroblastic tumor. However, the associated toxicity poses a significant challenge to its use. To mitigate this issue, a novel dry powder inhalation formulation was developed using Crizotinib-loaded polyethylene glycol-based polymeric nanoparticles (NPs). These nanoparticles were created through a nanoprecipitation approach and improved employing central composite design. The capabilities of the formulation were assessed with Anderson Cascade Impactor, revealing a fine particle fraction of 56.2% and a mass median aerodynamic diameter of around 1.5 μm, indicating appropriate aerodynamic characteristics for inhalation. Key properties of the optimized nanoparticles included Encapsulation efficiency (82.3%, Zeta potential (-31.9 mV), Particle size (167 nm), Polydispersity index (0.462) and Release efficiency (60.6%) In vitro studies indicated that the polymeric nanoparticles exhibited greater anticancer activity compared to free Crizotinib. Additional characterization using techniques like XRD, DSC, FTIR, and SEM confirmed that the polymeric nanoparticle formulation has promising physicochemical properties, suggesting it could enhance local drug delivery and efficacy in lung cancer treatment while potentially reducing systemic toxicity.

IntroductionBioaerosols are among pollutants that impair indoor air quality in schools and have been associated with increased respiratory morbidities. Knowledge of bioaerosols’ sizes and the likely deposition sites within the child’s respiratory tract are essential for the identification of associated risks. This study was designed to determine bioaerosols’ size distribution and associated respiratory morbidities among school pupils in Ibadan North Local Government Area (INLGA), Ibadan.MethodsA descriptive cross-sectional study design was adopted. In nine randomly selected public primary schools in INLGA, indoor air sampling (when occupied and unoccupied) was conducted thrice weekly for 3 months each in the wet and dry seasons, respectively. Airborne Bacterial Respirable Fraction (BRF) and Fungal Respirable Fraction (FRF) of aerodynamic diameter of 1.1–4.7 μm which corresponds to regions between the human primary bronchus and the alveolar duct were sampled using a six-stage cascade impactor. The BRF and FRF were estimated and dichotomised into high (>median) and low (≤median) categories. A standardized questionnaire was adapted to elicit information from 554 randomly selected pupils on socio-demographic characteristics and self-reported respiratory morbidities. Data were analyzed using descriptive and inferential statistics at α0.05.ResultsMedian BRF and FRF during the wet season (2,890 and 283 cfu/m3) were significantly higher than dry season (1,661 and 196 cfu/m3), respectively and above WHO standards. Median BRF and FRF were significantly higher when classrooms were occupied (3,906 and 230 cfu/m3) than unoccupied (2,800 and 214 cfu/m3), respectively. About 67.5% of total bacterial and 77.8% fungal aerosols were respirable fractions. Age of pupils was 10.8 ± 1.35 years and 57.4% were males. Exposure to high BRF and FRF was significantly associated with current rhinitis (aOR = 1.78, 95%CI: 1.11–2.85 and aOR = 1.83, 95%CI: 1.14–2.93) and current wheeze (aOR = 2.77, 95%CI: 1.73–4.43 and aOR = 1.88, 95%CI: 1.18–3.00), respectively. Male pupils were more likely to experience current rhinitis (aOR = 1.09, 95%CI: 1.15–1.58) and current wheeze (aOR = 1.11, 95%CI: 1.22–1.62) than females.ConclusionExposure to high levels of respirable bacterial and fungal fractions was associated with respiratory health outcomes among pupils.

Abstract Introduction It is unknown if positive airway pressure (PAP) devices are a potential reservoir of infectious microbes. We aimed to develop air sampling methodology for a PAP device under pressurised conditions, and to validate it using a limit of detection (LoD) technique, with concurrent viability and molecular assessment. Methods Exploratory methodology was used to assess pressurised airflow from PAP devices under conditions of intentional contamination with Pseudomonas aeruginosa (PA) or Escherichia coli (EC). Comparison between Anderson Cascade Impactor and a simple underwater broth methodology occurred for feasibility. The LoD methodology was used to find the lowest concentration of bacteria that was recoverable on culture (growth) vs molecular (16S rRNA gene sequencing) to ascertain detection of bacteria below the threshold of growth. Then, deliberate inoculation of device sites with PA was used to model the inhalation hazard of real-world contamination (air inlet, outlet, humidifier, and post-machine circuit). Results A model using intra-circuit nebulised bacteria determined LoD at 0.5McF (1.5 x 10^8 CFU/ml) for EC and 1.5 x 10^7 CFU/mL for PA. No viable cultures were detected at concentrations below the threshold of detection, or by inoculation at various device sites. Detection of airborne bacteria was only possible using nebulisation of organism in high concentrations unlikely to occur in real-world situations. Discussion Under normal operating conditions, recovery of viable bacteria did not occur. Hostility of airflow conditions may govern the non-viability of identified molecular isolates below the LoD. This study demonstrates non-survivability of two common bacteria with clinically relevant PAP settings.

Abstract. Ultrafine particles (diameter of less than 100 nm) are primary suspects for enhanced negative health effects on humans. Measuring the chemical composition and physical properties of ultrafine particles online, continuously, and accurately is particularly challenging because of their typically low mass concentration (PM0.1) and susceptibility to interference from larger particles. The few past PM0.1 chemical composition measurement studies have used cascade impactors and at least a daily temporal resolution. In this study, we perform, for the first time, high-temporal-resolution measurements of the composition and sources of PM0.1 using an aerodynamic aerosol classifier (AAC) to separate PM0.1 from larger particles, integrated with other instruments. These include a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS, for organics, sulfate, nitrate, ammonium, and chloride), a single-particle soot photometer (SP2-XR, for black carbon), and an Xact625i (for elements). Ambient PM0.1 composition measurements were conducted in a suburban area in Greece to test the system. The hourly PM0.1 levels varied from 0.4 to 1.5 µg m−3, with an average of 0.7 µg m−3. Most of the PM0.1 (45 %) was organic aerosol (OA). On average, sulfates contributed 14 %, ammonium contributed 7 %, nitrate contributed 3 %, and black carbon contributed 4 % to PM0.1. Calcium (Ca) showed a surprising high average contribution to PM0.1 (18 %). The rest of the detected elements were Fe, K, Zn, and Ti, contributing 7 % together. Source apportionment analysis showed that most of the PM0.1 OA during this summertime period was oxygenated OA (90 %), with 70 % being less oxidized and 20 % being more oxidized, while only 10 % was fresh hydrocarbon-like OA.

Determination of the radon progeny activity size distribution at different types of workplaces.

Assessment of particle-bound PFAS in ambient air from a coastal urban environment in South Florida.

A drone-based rotating cascade impactor for single-particle analysis: Advancing aerosol mixing state research

Background: In spite of efforts to eradicate tuberculosis (TB), TB remains the deadliest infectious disease in the world; there is an urgent need for a thermostable, noninvasive TB vaccine suitable for distribution in the developing world. Spray-dried versions of a clinical-stage TB vaccine, ID93 + GLA-SE, are currently undergoing testing in baboons in both pulmonary and intranasal versions. We developed manufacturing processes and delivery systems to achieve delivery of each version to its intended site of action while avoiding off-target deposition. Methods: Pulmonary ID93 + GLA-SE was manufactured in a custom research-scale spray dryer. Delivery efficiency using a custom intratracheal insufflator was measured gravimetrically, and aerodynamic performance was evaluated via cascade impaction. Intranasal ID93 + GLA-SE was manufactured in a pilot-scale spray dryer. In vitro regional deposition in the Alberta Idealized Nasal Inlet, measured by LC-MS/MS, was used as a surrogate for aerodynamic performance; total deposition was used to calculate a total delivered dose. For both powders, ID93 antigen content was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and GLA-SE adjuvant content was assessed via HPLC. Results: No substantial processing losses of the antigen or adjuvant were observed after spray drying in either formulation. For the pulmonary powder, the emitted dose exiting the endotracheal tube across three tube sizes ranged from 15.9% to 21.4% of the nominal dose; for the 8 mm tube size, the emitted dose mass median aerodynamic diameter was 5.3 µm, which was deemed suitable for pulmonary administration. For the intranasal powder, the delivered dose was 88% ± 2% of nominal, and in vitro deposition in the posterior nasal cavity was 63% ± 10% of the emitted dose, with minimal anticipated lung deposition. Conclusions: Pulmonary and intranasal spray-dried ID93 + GLA-SE powders were successfully manufactured. The proposed dosing systems are expected to achieve exclusive pulmonary or intranasal delivery to nonhuman primates while requiring only a moderate amount of powder.

The multi-stage cascade impactor (CI) is the recognized apparatus for the characterization of the aerodynamic particle size distribution (APSD) of aerosols emitted from all classes of orally inhaled products. There is presently a mixed level of understanding in the community of those evaluating inhaler performance about the fundamentals of how these apparatuses accomplish their particle size fractionation and therefore how to analyze their data in a technically correct and meaningful manner. The purpose of this article, therefore, is first to set out how the CI functions from the standpoint of the underlying physical processes associated with inertial size fractionation. The explanation of these size fractionation processes describes the relationship of the mass of active pharmaceutical ingredient to particle aerodynamic size. Second, based on these fundamentals, a detailed analysis is provided in support of calculating in a technically correct manner the cascade impactor-derived estimation of metrics describing the APSD. In a comprehensive Supplemental Information packet, the underlying mathematical principles are explained that govern both arithmetic and geometric forms of the traditional assumed shapes that the APSD may take when deriving measures in support of inhaler performance assessments.

Background The Global Initiative for Asthma (GINA) recommended using spacers or valved holding chambers to counter the common problems of poor pressurized metered dose inhaler (pMDI) technique. However, many subjects avoid using conventional spacers because they are bulky and inconvenient to carry around in public. Objective We aimed to compare the novel, MDI PLUS® spacer, with AeroChamber2go™ on their in vitro and in vivo aerosol performance, as well as their user training requirements. Methods In vitro, aerosol characteristics were assessed using an Andersen cascade impactor at 28.3 L/min with Ventolin® pMDI (5 puffs, 100 µg/puff); HPLC quantified drug deposition on each stage. In vivo, 20 asthmatic subjects received 500 µg salbutamol via pMDI alone, and pMDI + AeroChamber2go™ or MDI PLUS®. Urine samples were collected at 30 min and cumulatively over 24 h after inhaler use, and salbutamol samples were extracted and assessed using HPLC. Ex vivo delivery and user inhaler mastery were also assessed. Results The fine-particle dose increased from 94.98 µg (pMDI alone) to 128.45 µg with AeroChamber2go™ and 130.04 µg with MDI PLUS®, while the fine-particle fraction rose from 26.58% to 65.72% and 67.19%, respectively (p < .05). Thirty-minute urinary salbutamol excretion nearly doubled with both the MDI PLUS® and the AeroChamber2go, whereas systemic bioavailability over 24 h was significantly reduced from 143.35 µg with pMDI alone to approximately 60 µg with either device (p < .01). Notably, MDI PLUS required the fewest training sessions to master (1.03, p < .05). Conclusions Both the MDI PLUS® and the AeroChamber2go™ significantly enhanced pulmonary delivery and reduced systemic exposure compared to pMDI alone, while MDI PLUS® might potentially show a superior ease of use. These findings support the adoption of either device to optimize inhaler therapy.

Background: The "Miller" design of mixing inlet (MI) enables a cascade impactor to operate at a constant flow rate while the orally inhaled product-on-test is evaluated at varying flow rates by controlling the flow of air via its side-arm. Study Purpose: As part of the European Pharmaceutical Aerosol Group (EPAG) Impactor subgroup, we report a cross-industry experimental investigation by five organizations to determine internal losses of different inhaler-generated aerosolized medications within commercially available MIs, focusing on pharmacopeial methods for product testing. Methods: Evaluations were undertaken of solution and suspension formulations delivered by pressurized metered dose inhalers (pMDIs), passive dry powder inhalers (DPIs), and compressed air-jet and vibrating mesh nebulizers. Four different apparatuses were evaluated at different constant air flow rates entering the MI side arm. The nebulizers were tested utilizing a variable adult flow profile generated by a breathing simulator. Results: Losses within the MI were generally <5%, expressed as a percentage of the delivered mass of active pharmaceutical ingredient (API) ex-inhaler. These losses were sufficiently small that they can in most cases be accommodated within the allowance of ±5% OIP label claim emitted mass/actuation in the pharmacopeial compendia for total internal losses for aerodynamic particle size distribution (APSD) determination. However, corresponding average losses were between 2.8% and 5.2% of the mass of API presented to the MI for the blister-based DPIs. APSD-derived measures were largely unaffected by the magnitude of pressurized air flow up to 60 L/min to the side-arm of the MI, except for the solution-formulated pMDI, where increasing flow rate was associated with reduced mass median aerodynamic diameter and increased geometric standard deviation, suggestive of a dependency related to ethanol co-solvent evaporation rate. Conclusions: MI loss evaluation should be considered an important part of method development to minimize internal losses of the aerosolized medication being sampled.

A method was developed to sample molten salts by spargingto generateand transport aerosols to an isolated instrument for compositionalanalysis by laser-induced breakdown spectroscopy (LIBS). Real-timemonitoring of molten salt composition is critical to developing moltensalt nuclear reactors, which offer enhanced safety and efficiency.In this article, the sparge sampling method is described and comparedwith sampling using a Collison nebulizer. The size distribution andtransport of aerosols produced from molten eutectic NaNO3–KNO3 salt were compared for multiple gas flowrates (75–1200 mL min–1) and transport distances(0.68–2.61 m). Both methods produced aerosols ranging from0.5 to 5.0 μm determined using a cascade impactor. Aerosolswere effectively transported without pre- or trace-heating of gaslines, but transport efficiency was reduced by the formation of agglomerates.Sparge sampling was found to use less sample and less gas than a Collisonnebulizer while producing a more concentrated aerosol stream (up to5 μg L–1). The effects of laser energy anddelay time on the signal quality of LIBS measurements of these aerosolswere also studied. High energy and short delay times were found toenhance signal and repeatability, whereas signal-to-background andsignal-to-noise ratios were highest at low energy and longer delaytimes. The capabilities of this system for online monitoring of moltensalts were demonstrated with calibrations for Sr and Li with relativestandard deviations of 2.6% and 1.5% and limits of detection of 380and 180 μg g–1, respectively.

There is growing demand for simplified collection of the fine particle dose (FPD, mass of particles less than 5µm in diameter) of orally inhaled drug products (OIDPs) for physicochemical characterization. Dissolution kinetics of the FPD are of particular interest in quality control, bioequivalence studies, and the development of branded and generic OIDPs. The Fast Screening Impactor (FSI) is an abbreviated impactor for collecting the FPD of OIDPs, but there is concern that the FSI overrepresents the FPD due to particles larger than the cutoff traveling past the impactor stage. This issue is most observable when testing dry powder inhalers (DPIs) due to their common use of coarse carrier particles. In this work, we evaluated design modifications to the pre-separator inserts of the FSI to determine their effect on the FPD collection from a commercially available DPI. 3-dimensional (3D) printed FSI inserts were designed to improve impactor cutoff efficiency and collect a FPD equivalent to that collected using full-resolution cascade impactors. Modified FSI inserts were 3D-printed with the nozzle length (T) and baseplate-to-nozzle distance (S) varied while keeping other design parameters, including nozzle diameter (D), the same as the manufacturer's specifications to determine the impact of design parameters on impactor cutoff efficiency. We found that increasing the T/D ratio to 1.0 showed little cutoff improvement for the standard pre-separator insert but decreasing the S/D ratio to 1.0 improved the impactor cutoff characteristics of the FPD insert, designed for a 5µm cutoff at a 60 L/min flowrate. Our improved 3D-printed FPD insert collected an FPD that more closely matched the Anderson Cascade Impactor (ACI) and the Next Generation Impactor (NGI) FPD results. This work evaluated key design parameters necessary for improving the cutoff efficiency of pre-separator inserts to collect FPD more accurately when compared to full-resolution cascade impactors.

Background: Off-label nebulization of tranexamic acid (TXA) solution is common practice for the treatment of hemoptysis. However, data regarding nebulization protocols, resulting aerodynamic parameters of the generated aerosol, and corresponding biopharmaceutical parameters are missing. The aim of this in vitro study was to investigate the aerosol characteristics of nebulized sterile, aqueous TXA solution. Methods: TXA solution 100 mg/mL was nebulized for 2 min by a multi-dose vibrating mesh nebulizer using 15 L/min and 30 L/min air flow rates. The generated aerosol was analyzed by a Next Generation Cascade Impactor. For each air flow rate, the mean Fine Particle Dose (FPD), Fine Particle Fraction (FPF), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard Deviation (GSD) were quantified. Results: Nebulization at 15 L/min air flow rate resulted in a MMAD of 6.68 ± 0.23 µm and GSD of 2.02 ± 0.16. The FPD &lt; 5 µm was 16.56 ± 0.45 mg, the FPF &lt; 5 µm 28.91 ± 3.40%. Nebulization at 30 L/min air flow rate revealed a MMAD of 5.18 ± 0.12 µm and GSD of 2.14 ± 0.10. The FPD &lt; 5 µm was 16.30 ± 1.38 mg, the FPF &lt; 5 µm 35.43 ± 0.59%. Conclusions: Nebulization of TXA 100 mg/mL solution by a specified vibrating mesh nebulizer generated an aerosol particle distribution and deposition pattern suitable for the treatment of hemoptysis with bronchial origin.

Current anti‐fibrotic therapeutics for idiopathic pulmonary fibrosis (IPF) slow disease progression but are non‐curative and have systemic side effects, promoting interest in therapies that can repolarize macrophages away from their pro‐fibrotic phenotype. While yeast beta‐glucan (YBG) offers therapeutic potential in reprogramming macrophages toward an anti‐fibrotic phenotype, YBG processing must be optimized to promote inhalability while preserving its biological activity. Herein, the biological and inhalation performance of YBG processed via Pressurized Gas eXpanded liquids technology (PGXTEC‐YBG) relative to conventionally spray‐dried YBG (SD‐YBG) is compared. The significantly smaller size and lower density of PGXTEC‐YBG relative to SD‐YBG result in a smaller aerodynamic diameter (3–4 µm) and double the fine particle fraction in cascade impaction studies, variables correlated with improved inhalability and thus deposition in the distal regions of the lung. Correspondingly, PGXTEC‐YBG shows an approximately double phagocytic index in vitro and enhanced suppression of CD206 expression and arginase‐1 activity, lower levels of macrophage stress, and comparable capacity for promoting pro‐inflammatory cytokine release in ex vivo murine precision cut lung slices relative to SD‐YBG. These findings highlight PGXTEC‐YBG's utility as a promising inhalable therapeutic that can offer improved delivery to the disease site while maintaining strong biological anti‐fibrotic effects and reduced systemic toxicity.

Background/Objectives: Chronic lung diseases are among the leading causes of death worldwide. In the treatment of these diseases, non-steroidal anti-inflammatory drugs can be effective. We have previously developed an excipient formulation alongside a modern manufacturing protocol, which we aim to further investigate. We have chosen two new model drugs, meloxicam (MX) and its water-soluble salt, meloxicam-potassium (MXP). The particles in dry powder inhaler (DPI) formulation were expected to have a spherical shape, fast drug release, and good aerodynamic properties. Methods: The excipients were poloxamer-188, mannitol, and leucine. The samples were prepared by spray drying, preceded by solution preparation and wet grinding. Particle size was determined by laser diffraction, shape by scanning electron microscopy (SEM), crystallinity by powder X-ray diffraction (PXRD), interactions by Fourier-transform infrared spectroscopy (FT-IR), in vitro drug dissolution by paddle apparatus, and in vitro aerodynamic properties by Andersen cascade impactor and Spraytec® device. Results: We achieved the proper particle size (<5 μm) and spherical shape according to laser diffraction and SEM. The XRPD showed partial amorphization. FT-IR revealed no interaction between the materials. During the in vitro dissolution tests, more than 90% of MX and MXP were released within the first 5 min. The best products exhibited an aerodynamic diameter of around 4 µm, a fine particle fraction around 50%, and an emitted fraction over 95%. The analysis by Spraytec® supported the suitability for lung targeting. Conclusions: The developed preparation process and excipient system can be applied in the development of different drugs containing DPIs.