Powder Aerosol Research Articles

Feasibility of a High-Dose Inhaled Indomethacin Dry Powder with Dual Deposition for Pulmonary and Oral Delivery

In this study we have developed a high-dose dry powder inhaler formulation of indomethacin using a novel approach to carrier-based formulations. Specifically, larger drug particles serve as the carrier for the smaller micronized drug particles, such that an inhaled dose is combined with an oral dose. To study this system, the aerosol performance of a standard indomethacin–lactose formulation was compared to carrier-free micronized indomethacin and a drug-as-carrier formulation (a micronized indomethacin–coarse indomethacin blend). Indomethacin with lactose showed a very poor aerosol performance, indicating high adhesion between the drug and carrier. The performance of the carrier-free micronized drug was significantly better, indicating low cohesion. Coarse drug particles as a carrier allowed improved powder flow and aerosol performance while also providing a potential secondary route of absorption of indomethacin, namely oral. An optimal formulation ratio of 1:1 (w/w) fine indomethacin–coarse indomethacin was developed in this study.

Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) – Part II: In vivo Efficacy Testing in a Rabbit Surfactant Washout Model

PurposeSurfactant therapy incorporates liquid bolus instillation via endotracheal tube catheter and a mechanical ventilator in preterm neonates with respiratory distress syndrome (RDS). Aerosolized surfactants have generated interest and conflicting data on the efficacy of phospholipid (PL) dose requirements. We developed and characterized a synthetic lung surfactant excipient enhanced growth (SLS-EEG) dry powder aerosol product. In this study, we compare the in vivo performance of the new aerosol product with standard-of-care liquid instillation.MethodsJuvenile rabbits were sedated, anesthetized, intubated, and ventilated. Endogenous surfactant was depleted via whole lung lavage. Animals received either a standard dose of liquid Curosurf (200 mg PL/kg) instilled via a tracheal catheter, SLS-EEG powder aerosol (60 mg device loaded dose; equivalent to 24 mg PL/kg), or sham control. Gas exchange, lung compliance, and indices of disease severity were recorded every 30 min for 3.5 h and macro- and microscopy images were acquired at necropsy.ResultsWhile aerosol was administered at an approximately tenfold lower PL dose, both liquid-instilled and aerosol groups had similar, nearly complete recoveries of arterial oxygenation (PaO2; 96–100% recovery) and oxygenation index, and the aerosol group had superior recovery of compliance (P < 0.05). The SLS-EEG aerosol group showed less lung tissue injury, greater uniformity in lung aeration, and more homogenous surfactant distribution at the alveolar surfaces compared with liquid Curosurf.ConclusionsThe new dry powder aerosol SLS product (which includes the delivery strategy, formulation, and delivery system) has the potential to be a safe, effective, and economical alternative to the current clinical standard of liquid bolus surfactant instillation.

Development of a proliposomal pretomanid dry powder inhaler as a novel alternative approach for combating pulmonary tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue as public health concerns. Inhaled drug therapy for TB has substantial benefits in combating the causal agent of TB (Mycobacterium tuberculosis). Pretomanid is a promising candidate in an optional combined regimen for XDR-TB. Pretomanid has demonstrated high potency against M. tuberculosis in both the active and latent phases. Conventional spray drying was used to formulate pretomanid as dry powder inhalers (DPIs) for deep lung delivery using a proliposomal system with a trehalose coarse excipient to enhance the drug solubility. Co-spray drying with L-leucine protected hygroscopic trehalose in formulations and improved powder aerosolization. Higher amounts of L-leucine (40–50 % w/w) resulted in the formation of mesoporous particles with high percentages of drug content and entrapment efficiency. The aerosolized powders demonstrated both geometric and median aerodynamic diameters < 5 µm with > 90 % emitted dose and > 50 % fine particle fraction. Upon reconstitution in simulated physiological fluid, the proliposomes completely converted to liposomes, exhibiting suitable particle sizes (130–300 nm) with stable colloids and improving drug solubility, leading to higher drug dissolution compared to the drug alone. Inhalable pretomanid showed higher antimycobacterial activity than pretomanid alone. The formulations were safe for all broncho-epithelial cell lines and alveolar macrophages, thus indicating their potential suitability for DPIs targeting pulmonary TB.

Different Carriers for Use in Dry Powder Inhalers: Characteristics of Their Particles.

In contemporary times, there has been a rise in the utilization of dry powder inhalers (DPIs) in the management of pulmonary and systemic diseases. These devices underwent a swift advancement in terms of both the equipment utilized and the formulation process. In this review, the carrier physicochemical characteristics that influence DPI performance are discussed, focusing its shape, morphology, size distribution, texture, aerodynamic diameter, density, moisture, adhesive and detachment forces between particles, fine carrier particles, and dry powder aerosolization. To promote the deposition of the active principal ingredient deep within the pulmonary system, advancements have been made in enhancing these factors and surface properties through the application of novel technologies that encompass particle engineering. So far, the most used carrier is lactose showing some advantages and disadvantages, but other substances and systems are being studied with the intention of replacing it. The final objective of this review is to analyze the physicochemical and mechanical characteristics of the different carriers or new delivery systems used in DPI formulations, whether already on the market or still under investigation. [Figure: see text].

Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) – Part I: In Vitro Testing and Characterization

PurposeImproving the deep lung delivery of aerosol surfactant therapy (AST) with a dry powder formulation may enable significant reductions in dose while providing improved efficacy. The objective of Part I of this two-part study was to present the development of a new dry powder aerosol synthetic lung surfactant (SLS) product and to characterize performance based on aerosol formation and realistic in vitro airway testing leading to aerosol delivery recommendations for subsequent in vivo animal model experiments.MethodsA new micrometer-sized SLS excipient enhanced growth (EEG) dry powder formulation was produced via spray drying and aerosolized using a positive-pressure air-jet dry powder inhaler (DPI) intended for aerosol delivery directly to intubated infants with respiratory distress syndrome (RDS) or infant-size test animals.ResultsThe best-case design (D2) of the air-jet DPI was capable of high emitted dose (> 80% of loaded) and formed a < 2 µm mass median aerodynamic diameter (MMAD) aerosol, but was limited to ≤ 20 mg mass loadings. Testing with a realistic in vitro rabbit model indicated that over half of the loaded dose could penetrate into the lower lung regions. Using the characterization data, a dose delivery protocol was designed in which a 60 mg total loaded dose would be administered and deliver an approximate lung dose of 14.7–17.7 mg phospholipids/kg with a total aerosol delivery period < 5 min.ConclusionsA high-efficiency aerosol SLS product was designed and tested that may enable an order of magnitude reduction in administered phospholipid dose, and provide rapid aerosol administration to infants with RDS.

Inhalable tobramycin EEG powder formulation for treating Pseudomonas aeruginosa-induced lung infection

Pulmonary delivery of antibiotics is an effective strategy in treating bacterial lung infection for cystic fibrosis patients, by achieving high local drug concentrations and reducing overall systemic exposure compared to systemic administration. However, the inherent anatomical lung defense mechanisms, formulation characteristics, and drug-device combination determine the treatment efficacy of the aerosol delivery approach. In this study, we prepared a new tobramycin (Tobi) dry powder aerosol using excipient enhanced growth (EEG) technology and evaluated the in vitro and in vivo aerosol performance. We further established a Pseudomonas aeruginosa-induced lung infection rat model using an in-house designed novel liquid aerosolizer device. Notably, novel liquid aerosolizer yields comparable lung infection profiles despite administering 3-times lower P. aeruginosa CFU per rat in comparison to the conventional intratracheal administration. Dry powder insufflator (e.g. Penn-Century DP-4) to administer small powder masses to experimental animals is no longer commercially available. To address this gap, we developed a novel rat air-jet dry powder insufflator (Rat AJ DPI) that can emit 68–70 % of the loaded mass for 2 mg and 5 mg of Tobi-EEG powder formulations, achieving a high rat lung deposition efficiency of 79 % and 86 %, respectively. Rat AJ DPI can achieve homogenous distribution of Tobi EEG powder formulations at both loaded mass (2 mg and 5 mg) over all five lung lobes in rats. We then demonstrated that Tobi EEG formulation delivered by Rat AJ DPI can significantly decrease CFU counts in both trachea and lung lobes at 2 mg (p < 0.05) and 5 mg (p < 0.001) loaded mass compared to the untreated P. aeruginosa-infected group. Tobi EEG powder formulation delivered by the novel Rat AJ DPI showed excellent efficiencies in substantially reducing the P. aeruginosa-induced lung infection in rats.

Powder aerosol deposited calcium cobaltite as textured P-type thermoelectric material with power factors approaching single crystal values

In this work, the thermoelectric material calcium cobaltite Ca3Co4O9 (CCO), a promising p-type conducting thermoelectric oxide with anisotropic properties, was processed by the powder aerosol deposition method (PAD) to form a dense ceramic CCO film with a thickness in the µm range. The prepared films were characterized regarding their microstructure and thermoelectric properties between room temperature and 900 °C. After heat treatment at 900 °C, the CCO PAD film in-plane shows excellent properties in terms of electrical conductivity (280 S/cm at 900 °C) and Seebeck coefficient (220 µV/K at 900 °C). The calculated power factor in-plane (ab) reaches with 1125 µW/(m K2) 40 % of the single crystal value, surpassing the known-properties of CCO bulk ceramics. Examination of the microstructure shows a strong fiber texture of the film as well as a strong coarsening of the grains during the first heat treatment up to 900 °C.

Effect of Magnesium Stearate and Fines on Delivery of Dry Powder for Inhalation using Sucrose as a Carrier

Typically, lactose is utilised as carrier in Dry Powder Inhaler commercially. However, with the widening scope of DPI in therapeutic categories other than COPD and asthma, a need for the alternate carrier is arising. In this study, we used sucrose, a non-reducing sugar, as an alternate carrier. Effect of addition of fines and magnesium stearate was studied on powder flow properties and aerosolization performance. The air jet milling technique was used to generate sucrose fines. DSC and XRD studies showed no change in sucrose polymorph upon micronization. Levosalbutamol sulphate was used as a model drug, powder blends were prepared by low shear tumbling type blender. Powder formulations were studied for PSD, blend homogeneity, and flow properties. The percentage of particles smaller than 5 microns rose when fines were added as indicated by PSD data. SEM study revealed that the added fines get adsorbs on the coarse carrier, thus minimizing the adhesive interactions between drug and coarse carrier. In-vitro deposition was studied using low and high resistance devices on glass Twin Stage Impinger (TSI). Addition of fines and the magnesium stearate improves aerosolization performance showing higher Fine Particle Fraction (FPF) by almost 2 folds than the formulation containing coarse carrier alone.

Lung surfactant inhibition and cytotoxicity at the air-liquid interface of dry particle aerosols

Industrial processes generate chemicals that have the potential to be aerosolized and inhaled by workers, thereby posing health risks. Traditional toxicology methods employing animal models cannot keep up with the pace of emerging hazards. Nascent in vitro practices face challenges regarding translatability to the real world. To address this critical gap, this study demonstrated a workflow utilizing aerosol characterization in a more realistic exposure scenario: dry powder aerosolization onto the air-liquid interface of lung cells. This study delves into biophysical aspects of lung function by examining lung surfactant inhibition. A set of particulates, including aluminum, aluminum oxide, carbon nanotubes, diesel particulate matter, and colloidal silica, was selected for investigation. Particles were in the respirable regime, with mean aerodynamic diameters ranging from 111 to 162 nm by number and 369–2884 nm by mass. Carbon nanotubes and colloidal silica were identified as surfactant inhibitors. Aerosol doses reduced cell viability, up to 38%, with the most pronounced effects observed in response to exposure to aluminum and diesel particulate matter. Dry particle exposure at the air-liquid interface shows promise even at low doses, compared with nebulization or inoculation to submerged cultures. Our findings underscore the potential of this innovative approach for assessing the hazards of aerosolized particulates and emerging contaminants, offering a more accurate representation of real-world exposure scenarios.

Powder Aerosol Deposition and Polymers: Is There Hope for a Common Future?

Polymer–ceramic composites (PCCs) are promising functional materials with applications in energy technology, microelectronics, sensor technology, protective coatings, wastewater treatment or for biomedical purposes. Unfortunately, ceramics require high‐temperature sintering, while polymers only have a limited thermal stability. Therefore, PCC fabrication is quite complex and requires strict process control. This severely limits the efficiency and economy of the process and the reproducibility of the desired materials properties. Powder aerosol deposition (PAD) is a spray‐coating process in which ceramic powders are accelerated by a pressure difference using a carrier gas. They are then deposited as nanocrystalline, dense coatings onto a substrate without the need for additional sintering. In the current PAD research, the focus is ceramic powders. Yet there are also examples of polymer and ceramic particles that have been codeposited. Much of this works is trial‐and‐error, and a general concept for deposition of PCCs by PAD is not yet available. This review revisits the fundamentals of PAD and the most important process parameters that were studied experimentally and in silico. It connects these with recent work on the combination of polymers and ceramics in the PAD process to highlight and evaluate the future of this field from a polymer science perspective.

Dry powder inhalation containing muco-inert ciprofloxacin and colistin co-loaded liposomes for pulmonary P. Aeruginosa biofilm eradication

Pseudomonas aeruginosa (PA), a predominant pathogen in lung infections, poses significant challenges due to its biofilm formation, which is the primary cause of chronic and recalcitrant pulmonary infections. Bacteria within these biofilms exhibit heightened resistance to antibiotics compared to their planktonic counterparts, and their secreted toxins exacerbate lung infections. Diverging from traditional antibacterial therapy for biofilm eradication, this study introduces a novel dry powder inhalation containing muco-inert ciprofloxacin and colistin co-encapsulated liposomes (Cipro-Col-Lips) prepared using ultrasonic spray freeze drying (USFD) technique. This USFD dry powder is designed to efficiently deliver muco-inert Cipro-Col-Lips to the lungs. Once deposited, the liposomes rapidly diffuse into the airway mucus, reaching the biofilm sites. The muco-inert Cipro-Col-Lips neutralize the biofilm-secreted toxins and simultaneously trigger the release of their therapeutic payload, exerting a synergistic antibiofilm effect. Our results demonstrated that the optimal USFD liposomal dry powder formulation exhibited satisfactory in vitro aerosol performance in terms of fine particle fraction (FPF) of 44.44 ± 0.78 %, mass median aerodynamic diameter (MMAD) of 4.27 ± 0.21 μm, and emitted dose (ED) of 99.31 ± 3.31 %. The muco-inert Cipro-Col-Lips effectively penetrate the airway mucus and accumulate at the biofilm site, neutralizing toxins and safeguarding lung cells. The triggered release of ciprofloxacin and colistin works synergistically to reduce the biofilm’s antibiotic resistance, impede the development of antibiotic resistance, and eliminate 99.99 % of biofilm-embedded bacteria, including persister bacteria. Using a PA-beads induced biofilm-associated lung infection mouse model, the in vivo efficacy of this liposomal dry powder aerosol was tested, and the results demonstrated that this liposomal dry powder aerosol achieved a 99.7 % reduction in bacterial colonization, and significantly mitigated inflammation and pulmonary fibrosis. The USFD dry powder inhalation containing muco-inert Cipro-Col-Lips emerges as a promising therapeutic strategy for treating PA biofilm-associated lung infections.

Nanoscale colocalized thermal and chemical mapping of pharmaceutical powder aerosols

Inhalation of pharmaceutical aerosol formulations is widely used to treat respiratory diseases. Spatially resolved thermal characterization offers promise for better understanding drug release rates from particles; however, this has been an analytical challenge due to the small particle size (from a few micrometers down to nanometers) and the complex composition of the formulations. Here, we employ nano-thermal analysis (nanoTA) to probe the nanothermal domain of a pharmaceutical aerosol formulation containing a mixture of fluticasone propionate (FP), salmeterol xinafoate (SX), and excipient lactose, which is widely used to treat asthma and chronic obstructive pulmonary disease (COPD). Furthermore, atomic force microscopy-infrared spectroscopy (AFM-IR) and AFM force measurements are performed to provide nanochemical and nanomechanical information to complement the nanothermal data. The colocalized thermal and chemical mapping clearly reveals the surface heterogeneity of the drugs in the aerosol particles and demonstrates the contribution of the surface chemical composition to the variation in the thermal properties of the particles. We present a powerful analytical approach for in-depth characterization of thermal/chemical/morphological properties of dry powder inhaler particles at micro- and nanometer scales. This approach can be used to facilitate the comparison between generics and reference inhalation products and further the development of high-performance pharmaceutical formulations.

The Impact of Grain Growth on the Functional Properties in Room-Temperature Powder Aerosol Deposited Free-Standing (Ba,Ca)(Zr,Ti)O3 Thick Films

This study investigates the development of freestanding thick films (FSFs) of lead-free (Ba,Ca)(Zr,Ti)O3 and the role of grain growth on the electromechanical response. During deposition, room temperature powder aerosol deposition rapidly produces thick films with a nano-grain structure that limits the electromechanical properties. In this study, the films are removed from the substrate using a sacrificial buffering layer to avoid thermal treatment and allow for an initial as-processed state. Following this, FSFs were thermally treated at various annealing temperatures from 800 °C to 1400 °C to induce grain growth, which was characterized with scanning and transmission electron microscopy. X-ray diffraction revealed an increase in the crystallite size consistent with an increase in grain size and a decrease in internal residual stress. The temperature-dependent dielectric behavior and the large-field ferroelectric response were also characterized, revealing significant differences of the FSFs from the bulk properties.

Comparative study of the inhalation parameters of COPD patients through NEXThaler® and Ellipta® dry powder inhalers

The deposition of dry powder aerosol drugs depends on the inhalation parameters of the patients through the inhaler. These data are not directly measured in clinical practice. Their prediction based on the routinely measured spirometric data could help in choosing the appropriate device and optimizing the therapy. The aim of this study was to perform inhalation experiments to find correlations between inhalation parameters of COPD patients through two DPI devices and their native spirometric data, gender, age and disease severity. Another goal was to establish relationships between peak inspiratory flows through NEXThaler® and Ellipta® inhalers and their statistical determinants. Breathing parameters of 113 COPD patients were measured by normal spirometry and while inhaling through the two DPIs. Statistical analysis of the measured data was performed. The average values of peak inspiratory flow through the devices (PIFdev) were 68.4 L/min and 78.0 L/min for NEXThaler® and Ellipta®, respectively. PIFdev values were significantly higher for males than for females, but differences upon age, BMI and disease severity group were not significant. PIFdev values correlated best with their native spirometric counterparts (PIF) and linear relationships between them were revealed. Current results may be used in the future to predict the success of inhalation of COPD patients through DPI devices, which may help in the inhaler choice. By choosing the appropriate device-drug pair for each patient the lung dose can be increased and the efficiency of the therapy improved. Further results of the clinical study will be the subject of a next publication.

Development of Aerosol Dry Powder Chemotherapeutic-Loaded Microparticles for the Treatment of Lung Cancer

Lung cancer is the leading cause of cancer-related deaths worldwide, resulting in the highest mortality rates among both men and women with respect to all other types of cancer. Difficulties in treating lung cancer arise from late-stage diagnoses and tumor heterogeneity and current treatment involves a combination of chemotherapeutics, surgery, and radiation. Chemotherapeutics administered systemically can lead to undesirable side effects and severe off-site toxicity. For example, chronic administration of the chemotherapeutic doxorubicin (DOX) leads to cardiotoxicity, thereby limiting its long-term use. Systemic administration of the highly lipophilic molecule paclitaxel (PTX) is hindered by its water solubility, necessitating the use of solubilizing agents, which can induce side effects. Thus, in this investigation, formulations consisting of spray-dried microparticles (MP) containing DOX and PTX were produced to be administered as dry powder aerosols directly to the lungs. Acetalated dextran (Ac-Dex) was used as the polymer in these formulations, as it is a biocompatible and biodegradable polymer that exhibits pH-responsive degradation. Solid-state characterization revealed that DOX and PTX remained in solubility favoring amorphous states in the MP formulations and that both drugs remained thermally stable throughout the spray drying process. In vitro release studies demonstrated the pH sensitivity of the formulations due to the use of Ac-Dex, as well as the release of both therapeutics over the course of at least 48 h. In vitro aerosol dispersion studies demonstrated that both formulations exhibited suitable aerosol dispersion properties for deep lung delivery.Graphical

Particle aerosol generation and potential altering in airflow used for acute/repeated inhalation toxicity testing

Reproducible aerosol generation in combination with stable aerosol properties are essential prerequisites for compliant performance of acute or repeated inhalation toxicity tests of particulate materials according to OECD TG 403, 436, 412, or 413. A frequent problem of powder aerosol generation is the formation of coarse agglomerates with low shear resistance, which are beyond the tolerable size range but not detected by the prescribed aerodynamic measurement techniques by cascade impactor as the measurement conditions cause a disintegration into smaller fragments. But such agglomerates are observed during the transport to the inhalation chambers. These effects particularly apply to high mass concentrations and low-density powders, i.e., pyrogenic oxides. This study describes the transport influence in the airflow on the change of powder aerosols and on their respirability.A simplified short tube set-up was developed for the aerosol transport pre-tests, which allows the determination of the optimal aerosol formation conditions for the inhalation tests. The particles were measured with low shear using laser diffraction measurement or optical particle counters. The calculation of the aerodynamic particle sizes prescribed in the guidelines requires knowledge of the effective particle density of the porous aerosol particles. A practicable method for determining these is presented and described. In the outlook, first low concentration measurements show that clear agglomeration effects can also occur at particle concentrations around 20 mg/m³.

Mixed-Potential Ammonia Sensor Based on a Dense Yttria-Stabilized Zirconia Film Manufactured at Room Temperature by Powder Aerosol Deposition

Powder aerosol deposition (often abbreviated as PAD, PADM, or ADM) is a coating method used to obtain dense ceramic films at room temperature. The suitability of this method to obtain ammonia mixed-potential sensors based on an yttria-stabilized zirconia (YSZ) electrolyte that is manufactured using PAD and a V2O5–WO3–TiO2 (VWT)-covered electrode is investigated in this study. The sensor characteristics are compared with data from sensors with screen-printed YSZ solid electrolytes. The PAD sensors outperform those in terms of sensitivity with 117 mV/decade NH3 compared to 88 mV/decade. A variation in the sensor temperature shows that the NH3 sensitivity strongly depends on the sensor temperature and decreases with higher sensor temperature. Above 560 °C, the characteristic curve shifts from exponential to linear dependency. Variations in the water and the oxygen content in the base gas (usually 10% oxygen, 2% water vapor in nitrogen) reveal a strong dependence of the characteristic curve on the oxygen content. Water vapor concentration variations barely affect the sensor signal.

Towards More Precise Targeting of Inhaled Aerosols to Different Areas of the Respiratory System.

Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during the aerosolization of liquids or powders and the role of aerosol flow dynamics in the RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Through an analysis of existing technical limitations, selected strategies aimed at enhancing the effectiveness of targeted aerosol delivery to the RS have been identified and presented. These strategies also include the use of smart inhaling devices and systems with built-in AI algorithms.

Mechanical properties and water vapour corrosion behaviour of Al x CoCrFeNi high-entropy alloys.

Al x CoCrFeNi (x = 0.1, 0.5 and 1) high-entropy alloys (HEAs) were prepared using a spark plasma sintering (SPS) technique combined with aerosol powder. Their microstructure and phase constituents were characterized using an X-ray diffractometer and SEM, and their tensile properties, hardness and compactness were tested. The results show that the crystal structure of the Al x CoCrFeNi HEAs changed significantly with the Al content, from the original single face-centered cubic FCC phase (Al0.1CoCrFeNi) to an FCC + BCC structure (Al0.5CoCrFeNi), and then to FCC + BCC + sigma (σ) phase structures (AlCoCrFeNi). Chemical composition analysis showed that the crystal structure transformation was related to the segregation caused by the increased Al content. The hardness of the Al x CoCrFeNi HEAs increases with increasing Al content, and the hardness of AlCoCrFeNi reaches a maximum of 507.3 HV. The tensile properties of the alloy show a trend of first increasing and then decreasing with increasing Al content, and the yield strength, ultimate tensile strength and elongation of the Al0.5CoCrFeNi alloy reach maximum values of 527.4 MP, 943.3 MPa and 28.2%, respectively. The fracture mechanism of the Al0.1CoCrFeNi and Al0.5CoCrFeNi alloys is typical ductile fracture, while that of the AlCoCrFeNi alloy is cleavage fracture. The compactness of the alloy increases with the Al content. The samples were also subjected to high-temperature water vapour corrosion, and corrosion products such as Al3Fe5O12, CoCr2O4 and NiCr2O4 were found in the Al0.1 and Al0.5 alloys, whereas no oxide peaks were detected using XRD for the Al1 alloy. It was also presumed that a very thin alumina film was generated on the surface of the Al1 alloy, preventing the oxidation of the sample, in combination with the analysis of SEM, EDS and XPS behaviour.

Repurposing ebselen as an inhalable dry powder to treat respiratory tract infections

Respiratory tract infections (RTIs) are one of the leading causes of death globally, lately exacerbated by the increasing prevalence of antimicrobial resistance. While antimicrobial resistance could be overcome by developing new antimicrobial agents, the use of a safe repurposed agent having potent antimicrobial activity against various RTIs can be an efficient and cost-effective alternative to overcome the long and complex process of developing and testing new drugs. Ebselen, a synthetic organoselenium drug originally developed to treat noise-inducing hearing problems, has shown promising antimicrobial activity in vitro against several respiratory pathogens including viruses (e.g., SARS-CoV-2, influenza A virus) and bacteria (e.g., Mycobacterium tuberculosis, Streptococcus pneumoniae, and Staphylococcus aureus). Inhaled drug delivery is considered a promising approach for treating RTIs, as it can ensure effective drug concentrations at a lower dose, thereby minimizing the side effects that are often encountered by using oral or injectable drugs. In this study, we developed inhalable ebselen dry powder formulations using a spray-drying technique. The amino acids leucine, methionine, and tryptophan were incorporated with ebselen to enhance the yield and aerosolization of the dry powders. The amino acid-containing ebselen dry powders showed a better yield (37–56.4 %) than the amino acid-free formulation (30.9 %). All dry powders were crystalline in nature. The mass median aerodynamic diameter (MMAD) was less than 5 µm for amino acids containing dry powders (3–4 µm) and slightly higher (5.4 µm) for amino acid free dry powder indicating their suitability for inhalation. The aerosol performance was higher when amino acids were used, and the leucine-containing ebselen dry powder showed the highest emitted dose (84 %) and fine particle fraction (68 %). All amino acid formulations had similar cytotoxicity as raw ebselen, tested in respiratory cell line (A549 cells), with half-maximal inhibitory concentrations (IC50) between 100 and 250 μg/mL. Raw ebselen and amino acid-containing dry powders showed similar potent antibacterial activity against the Gram-positive bacteria S. aureus and S. pneumoniae with minimum inhibitory concentrations of 0.31 μg/mL and 0.16 μg/mL, respectively. On the other hand, raw ebselen and the formulations showed limited antimicrobial activity against the Gram-negative pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae. In summary, in this study we were able to develop amino-acid-containing inhalable dry powders of ebselen that could be used against different respiratory pathogens, especially Gram-positive bacteria, which could ensure more drug deposition in the respiratory tract, including the lungs. DPIs are generally used to treat lung (lower respiratory tract) diseases. However, DPIs can also be used to treat both upper and lower RTIs. The deposition of the dry powder in the respiratory tract is dependent on its physicochemical properties and this properties can be modulated to target the intended site of infection (upper and/or lower respiratory tract). Further studies will allow the development of similar formulations of individual and/or combination of antimicrobials that could be used to inhibit a number of respiratory pathogens.