Mass Mean Aerodynamic Diameter Research Articles

Development of Inhalable Spray Dried Nitrofurantoin Formulations for the Treatment of Emphysema

A central characteristic of emphysematous progression is the continuous destruction of the lung extracellular matrix (ECM). Current treatments for emphysema have only addressed symptoms rather than preventing or reversing the loss of lung ECM. Nitrofurantoin (NF) is an antibiotic that has the potential to induce lung fibrosis as a side effect upon oral administration. Our study aims to repurpose NF as an inhalable therapeutic strategy to upregulate ECM expression, thereby reversing the disease progression within the emphysematous lung. Spray-dried (SD) formulations of NF were prepared in conjunction with a two-fluid nozzle (2FN) and three-fluid nozzle (3FN) using hydroxypropyl methylcellulose (HPMC) and NF at 1:1 w/w. The formulations were characterized for their physicochemical properties (particle size, morphology, solid-state characteristics, aerodynamic behaviour, and dissolution properties) and characterized in vitro with efficacy studies on human lung fibroblasts. The 2FN formulation displayed a mass mean aerodynamic diameter (MMAD) of 1.8 ± 0.05 µm and fine particle fraction (FPF) of 87.4 ± 2.8% with significantly greater deposition predicted in the lower lung region compared to the 3FN formulation (MMAD: 4.4 ± 0.4 µm; FPF: 40 ± 5.8%). Furthermore, drug dissolution studies showed that NF released from the 2FN formulation after 3 h was significantly higher (55.7%) as compared to the 3FN formulation (42.4%). Importantly, efficacy studies in human lung fibroblasts showed that the 2FN formulation induced significantly enhanced ECM protein expression levels of periostin and Type IV Collagen (203.2% and 84.2% increase, respectively) compared to untreated cells, while 3FN formulations induced only a 172.5% increase in periostin and a 38.1% increase in type IV collagen. In conclusion, our study highlights the influence of nozzle choice in inhalable spray-dried formulations and supports the feasibility of using SD NF prepared using 2FN as a potential inhalable therapeutic agent to upregulate ECM protein production.

The effect of air purifiers and curtains on aerosol dispersion and removal in multi-patient hospital rooms.

Airborne transmission of disease is of concern in many indoor spaces. Here, aerosol dispersion and removal in an unoccupied 4-bed hospital room were characterized using a transient aerosol tracer experiment for 38 experiments covering 4 configurations of air purifiers and 3 configurations of curtains. NaCl particle (mass mean aerodynamic diameter ~3 μm) concentrations were measured around the room following an aerosol release. Particle transport across the room was 1.5-4min which overlaps with the characteristic times for significant viral deactivation and gravitational settling of larger particles. Concentrations were close to spatially uniform except very near the source. Curtains resulted in a modest increase in delay and decay times, less so when combined with purifiers. The aerosol decay rate was in most cases higher than expected from the clean air delivery rate, but the reduction in steady-state concentrations resulting from air purifiers was less than suggested by the decay rates. Apparently, a substantial (and configuration-dependent) fraction of the aerosol is removed immediately, and this effect is not captured by the decay rate. Overall, the combination of curtains and purifiers is likely to reduce disease transmission in multi-patient hospital rooms.

Inhalable Spray Dried Pro-Liposome Powder Containing Budesonide for Pulmonary Delivery

Budesonide is an anti-asthmatic agent which is used to control the symptoms of asthma like bronchospasm, oedema. Drug delivered to lung through inhalation will provide systemic and local drug delivery at lower dose in chronic and acute diseases. Dry powder inhalers are the best choice for targeting the anti-asthmatic drugs through pulmonary route. The objective of the present study is to prepare inhalable lipid coated budesonide microparticles by spray drying method so effective delivery of budesonide to the lungs can be achieved. The microparticles in the form of dry powder were obtained by either spray drying liposomal drug suspension or lipid drug suspension. The liposomes were initially prepared by solvent evaporation method using Hydrogenated Soyabean Phosphatidylcholine and Cholesterol (1:1, 1:2, 2:1) as lipid carrier and then spray dried later with mannitol as bulking agent at different lipid to diluent ratio (1:1.25, 1:2.5 & 1:5). The liposomes and liposomal dry powder were evaluated for vesicle size, % entrapment efficiency, in vitro drug release studies, powder characteristics, aerosol performance and stability studies. The liposomes prepared showed vesicle size (2-8 µm), Entrapment efficiency (92.22%) at lipid: drug ratio of (2.5:1) and observed 80.41 % drug release in 24 hrs. Pro-liposomes prepared by spray drying of liposomal drug suspension (LSD1) showed emitted dose, mean mass aerodynamic diameter, geometric standard deviation and fine particle fraction of 99.01%, 3.12 µm, 1.78 and 43.5% along with good powder properties. The spray dried powder was found to be stable at 4 ± 2 °C & 65% ± 5 % RH. The inhalable microparticles containing Budesonide containing lipid dry powder was successfully prepared by spray drying method that showed good aerodynamic properties and stability with mannitol as diluent. The microparticles produced with this novel approach could deliver drug on target via inhalation route and also ease manufacture process at large scale in fewer production steps.

Occupational exposure during metal additive manufacturing: A case study of laser powder bed fusion of aluminum alloy

Occupational exposure during metal additive manufacturing (Laser Powder Bed Fusion) using an aluminum alloy (AlSi10Mg) was assessed. Background aerosols before manufacturing, powder sieving, machine loading, manufacturing, machine unloading, powder unpacking, and machine cleaning were analyzed. Measurements were taken simultaneously at the source, in the near field, and on the operator during five manufacturing cycles. Aerosol measurement devices and physico-chemical techniques were used to determine the particle number or mass concentration (DiSCmini, core particle counter and sampling cassette), particle size distribution (NanoScan, optical particle detector and impactor), and the shape/size and chemical compositions of the inhalable particles (laser diffraction, inductively coupled plasma spectroscopy, scanning electron microscopy, energy dispersive X-ray microanalysis, and Brunauer–Emmett–Teller Method). The laser powder-bed fusion machine emitted in the additive manufacturing room an inhalable fraction of 2.37 ± 0.35 mg/m3, with an aerosol number concentration ranging from 2 × 104 to 105 #/cm3 and a mass mean aerodynamic diameter of 318 nm. A relatively low concentration level was observed in the near field of the machine with an aerosol number concentration of ∼104 #/cm3. A higher concentration level on the operator was attained during the unpacking and cleaning steps, showing an inhalable fraction of 1.73 ± 0.30 mg/m3. Al and Mg nanoparticles were aerosolized at the source (inside the laser powder-bed fusion machine) with a particle size distribution of 153 nm for Al and 117 nm for Mg and an aerosol number concentration reaching ten times that of the background aerosol level. The number or mass concentration of particles in the room atmosphere was increased to double that of the background aerosol level at specific workstations during manufacturing. Metal additive manufacturing is a source of potential occupational exposure to airborne metal nanoparticles. Particle-counting instruments showed high numbers of nanoparticles and some important peaks of particles ranging from 10 nm to 10 µm or larger at specific work tasks in the Additive Manufacturing (AM) environment. A multimetric approach was used to characterize the particle emissions resulting from this type of additive manufacturing.

Investigation of sorafenib tosylate loaded liposomal dry powder inhaler for the treatment of non-small cell lung cancer

The present hypothesis was to identify the potential of sorafenib tosylate (ST) loaded liposomal dry powder inhaler (ST-LDPI) for targeting non-small cell lung cancer (NSCLC). ST-LDPI was obtained by spray drying the ST loaded liposomes, evaluated for physicochemical properties and in vitro lung deposition by Andersen Cascade Impactor (ACI). Optimized liposomal formulation showed the particle size, zeta potential, encapsulation efficiency and drug content of 111.15 ± 1.03 nm, −29.87 ± 0.56 mV, 93.13 ± 1.11% and 84.47 ± 1.28%, respectively. Furthermore, ST-LDPI exhibited low density and good flowability. FESEM confirmed the spherical nature of particles with mean size of 3.15 ± 0.51 μm. The DSC and FTIR spectra revealed complete encapsulation of ST. Further, the PXRD showed reduced crystallinity ST. In vitro deposition demonstrated the fine particle fraction of 83.7 ± 0.09%, recovery of 95.43 ± 0.03%, mean mass aerodynamic diameter 3.15 ± 0.2 µm, geometric standard deviation 1.78 ± 0.15 µm and 85 ± 0.1% dispersibility. The In vitro drug release revealed biphasic release pattern, burst release in the first 6 h followed by sustained release up to 72 h. Hence this novel approach could be a targeted delivery of ST to the NSCLC treatment.

Development of solid lipid microparticles by melt-emulsification/spray-drying processes as carriers for pulmonary drug delivery

The aim of this study was to optimize the parameters of the complex melt-emulsification process coupled with the spray-drying, in order to maintain the balance between solid lipid microparticles (SLMs) powders aerodynamic performance and salbutamol sulfate release rate. Quality target product profile was identified and risk management and principal component analysis were used to guide formulation development. Obtained dry powders for inhalation (DPIs) were evaluated in terms of SLMs size distribution, morphology, true density, drug content, solid state characterization studies, in vitro aerosol performance and in vitro drug release. SLMs micrographs indicated spherical, porous particles. Selected powders showed satisfactory aerosol performance with a mean mass aerodynamic diameter of around 3 μm and acceptable fine particle fraction (FPF). Addition of trehalose positively affected SLMs aerodynamic properties. The results of in vitro dissolution testing indicated that salbutamol sulfate release from the tested SLMs formulations was modified, in comparison to the raw drug release. In conclusion, SLMs in a form of DPIs were successfully developed and numerous factors that affects SLMs properties were identified in this study. Further research is required for full understanding of each factor's influence on SLMs properties and optimization of DPIs with maximized FPFs.

Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms

PurposeNovel particle engineering approach was used in this study to generate high dose inhalable effervescent particles with synergistic effects against Pseudomonas aeruginosa biofilms.MethodsSpray dried co-amorphous salt of ciprofloxacin (CFX) and tartaric acid (TA) was prepared and coated with external layer of sodium bicarbonate and silica coated silver nanobeads. Design of experiments (DOE) was used to optimize physicochemical properties of particles for enhanced lung deposition.ResultsGenerated particles were co-amorphous CFX/TA showing that CFX lost its zwitterionic form and exhibiting distinct properties to CFX/HCl as assessed by FTIR and thermal analysis. Particles exhibited mass mean aerodynamic diameter (MMAD) of 3.3 μm, emitted dose of 78% and fine particle dose of 85%. Particles were further evaluated via antimicrobial assessment of minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentration (MBEC). MIC and MBEC results showed that the hybrid particles were around 3–5 times more effective when compared to CFX signifying that synergistic effect was achieved. Diffusing wave spectroscopy results showed that the silver containing particles had a disruptive effect on rheological properties as opposed to silver free particles.ConclusionsOverall, these results showed the potential to use particle engineering to generate particles that are highly disruptive of bacterial biofilms.

An Efficient and Cost-Effective Nose-Only Inhalational Chamber for Rodents: Design, Optimization and Validation.

The mainstay treatment of pulmonary disorders lies around the direct drug targeting to the lungs using a nebulizer, metered-dose inhaler, or dry powder inhaler. Only few inhalers are available in the market that could be used for inhalational drug delivery in rodents. However, the available rodent inhalers invariably require high cost and maintenance, which limits their use at laboratory scale. The present work, therefore, was undertaken to develop a simple, reliable, and cost-effective nose-only inhalation chamber with holding capacity of three mice at a time. The nebulized air passes directly and continuously from the central chamber to mouthpiece and maintains an aerosol cloud for rodents to inhale. Laser diffraction analysis indicated volume mean diameter of 4.02 ± 0.30μm, and the next-generation impactor studies, however, revealed mean mass aerodynamic diameter of 3.40 ± 0.27μm, respectively. An amount of 2.05 ± 0.20mg of voriconazole (VRC) was available for inhalation at each delivery port of the inhaler. In vivo studies indicated the deposition of 76.12 ± 19.50μg of VRC in the mice lungs when nebulized for a period of 20min. Overall, the developed nose-only inhalation chamber offers a reliable means of generating aerosols and successfully exposing mice to nebulization.

Occupational and Environmental Exposures and Their Role in Chronic Cough

To review the mechanisms by which occupational and environmental factors can contribute to chronic cough and to discuss the approach to diagnosis and management of these patients with review of recent publications in this area. An Expert Panel Report from the American College of Chest Physicians in 2016 addressed this topic. Recent publications improve understanding of mechanisms of effects. Inhaled dust, fumes, gases, and vapor can cause an irritant or inflammatory response in upper and lower airways leading to cough. Physico-chemical properties, exposure conditions, and host factors can influence effects. Particles ≤ 5 μm mass mean aerodynamic diameter are more likely to reach and affect the terminal lung units and the sinuses. Type I, type III, and type IV hypersensitivity responses contribute to diseases causing chronic cough. Improved diagnostic and immunologic tests are needed for many causative exposures such as home or work fungal exposures.

Toxic Effects of Particulate Matter Derived from Dust Samples Near the Dzhidinski Ore Processing Mill, Eastern Siberia, Russia.

Ambient particulate matter (PM) is associated with increased mortality and morbidity, an effect influenced by the metal components of the PM. We characterized five sediment samples obtained near a tungsten-molybdenum ore-processing complex in Zakamensk, Russia for elemental composition and PM toxicity with regard to pulmonary, vascular, and neurological outcomes. Elemental and trace metals analysis of complete sediment and PM10 (the respirable fraction, < 10µm mass mean aerodynamic diameter) were performed using inductively coupled plasma optical emission spectrometry (ICP-OES) and mass spectrometry (ICP-MS). Sediment samples and PM10 consisted largely of silicon and iron and silicon and sodium, respectively. Trace metals including manganese and uranium in the complete sediment, as well as copper and lead in the PM10 were observed. Notably, metal concentrations were approximately 10× higher in the PM10 than in the sediment. Exposure to 100µg of PM10 via oropharyngeal aspiration in C56BL/6 mice resulted in pulmonary inflammation across all groups. In addition, mice exposed to three of the five PM10 samples exhibited impaired endothelial-dependent relaxation, and correlative analysis revealed associations between pulmonary inflammation and levels of lead and cadmium. A tendency for elevated cortical ccl2 and Tnf-α mRNA expression was induced by all samples and significant upregulation was noted following exposure to PM10 samples Z3 and Z4, respectively. Cortical Nqo1 mRNA levels were significantly upregulated in mice exposed to PM10 Z2. In conclusion, pulmonary exposure to PM samples from the Zakamensk region sediments induced varied pulmonary and systemic effects that may be influenced by elemental PM composition. Further investigation is needed to pinpoint putative drivers of neurological outcomes.

Study on the Filtration Performance of the Baghouse Filters for Ultra-Low Emission as a Function of Filter Pore Size and Fiber Diameter.

The main objective of this study was to determine the effect of filter pore size and fiber diameter on the performance of the baghouse filters for ultra-low emission. In this study, three kinds of conventional polyester filter (depth filtration media) and two kinds of polytetrafluoroethylene membrane-coated polyester filter (surface filtration media), having various filter pore sizes and fiber diameters, were tested to determine the performance of static and dynamic filtration. In order to determine the static filtration performance, the filtration resistance and the filtration efficiency of the clean filter media were measured by the arrestance method. The dynamic filtration performance experiments were conducted to determine the dynamic resistances, dust depositions, and dynamic filtration efficiencies of the dust-containing filter media under the condition of dust airflow filtration through a pulse-cleaning cycle. In the dynamic filtration performance experiments, the size of 50% test dust was less than 2.5 μm, and the mass mean aerodynamic diameter of the dust was 1.5 μm. The filtration velocity was 2 m∙min−1, and the dust concentration was 18.4 g∙m−3. The static filtration performance experiments showed that the filter pore size greatly affected the filtration resistance and the filtration efficiency of the fabric structure of the surface filtration media. In the depth filtration media, the filtration efficiency and the filtration resistance of the fabric structure were improved when the filter pore size and the fiber diameter were smaller in magnitude. For all the five filter media, smaller the pore size of the filter media, greater was the filtration precision (for fine particles, such as PM2.5) of the fabric structure. In the dynamic filtration performance experiments, the filter pore size and the fiber diameter of the depth filtration media affected the dynamic filtration resistance and the dynamic filtration efficiency of the depth filtration media by affecting the deposition rate of dust in the depth filtration media; however, the filter pore size of the surface filtration media affected the blocking rate of dust in the membrane micropores, thus influencing the dynamic filtration resistance and the dynamic filtration efficiency of the surface filtration media.

Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.

Liposomal andrographolide dry powder inhalers for treatment of bacterial pneumonia via anti-inflammatory pathway

Andrographolide (AG) is a chemical entity from traditional Chinese herbs and its oral pills have been applied to the treatment of respiratory inflammation. Here we report pulmonary delivery of liposomal AG dry powder inhalers (LADPIs) for treatment of Staphylococcus aureus-induced pneumonia. AG liposomes were prepared with the injection method and then freeze-dried for preparation of LADPIs. AG liposomes were small and stable with a mean size of 77.91nm and a zeta potential of −56.13mV. Liposomes were well recovered after re-hydration of LADPIs that were suitable for pulmonary delivery with a mass mean aerodynamic diameter (MMAD) of 4.87μm and a fine particle fraction (FPF) of 23.03%. However, the MMAD and FPF of AG powders were 10.14μm and 8.37%, respectively. The in vitro anti-S. aureus effects of AG powders and LADPIs were investigated, but were not found. They were intratracheally sprayed into the rat lungs for treatment of S. aureus pneumonia. Surprisingly, LADPIs showed a stronger anti-S. aureus pneumonic effect in vivo, than AG at a ten-fold dose or than an antibiotic, penicillin. LADPIs significantly decreased many pro-inflammatory cytokines including TNF-α, IL-1. Furthermore, the phosphorylation of IκB-α in the nuclear factor-κB (NF-κB) pathway was also remarkably inhibited. AG regulated the immune reaction to maintain the antibacterial effect while downregulating inflammatory response so that AG showed a strong effect on bacterial pneumonia. LADPIs are a promising pulmonary delivery medicine for the treatment of bacterial pneumonia.

Development, In Vitro Characterization, Antitumor and Aerosol Performance Evaluation of Respirable Prepared by Self-nanoemulsification Method.

Poor water solubility and low oral bioavailability limit the clinical application of Erlotinib as an anticancer. For this purpose, we encapsulated erlotinib in the solid lipid nanoparticles (SLN) and designed a spray-dried dry powder inhalable (DPI) formulation. Erlotinib-loaded SLNs were prepared using self-nanoemulsifying and characterized for physicochemical properties. Pulmonary deposition of spray-dried DPI formulation was performed using Next Generation Impactor. The particle size and zeta potential of Erlotinib-loaded SLNs were 300 to 800 nm and -18 to -32 mV, respectively. High drug entrapment efficiency in the narrow range of 80-85% was achieved. Cytotoxicity results indicated that cell growth inhibition of free drug and drug loaded nanoparticles is dose- and time-dependent. Inhalable dry powders prepared from drug-loaded SLNs were found to have a fine particle fraction in the range of 6.92±0.99 -11.24±2.4%, mean mass aerodynamic diameter in the range of 4.52±0.1 to 6.67±0.5 µm. The findings revealed that the proposed inhalable dry powder formulation loaded with erlotinib SLN has potential in lung cancer therapy through pulmonary route.

Nanocrystals embedded in chitosan-based respirable swellable microparticles as dry powder for sustained pulmonary drug delivery

In this study, nanocrystals embedded in microparticles were designed to achieve sustained pulmonary drug delivery of hydrophobic drugs. Chitosan based microparticles were engineered to allow sustained drug release via swelling and mucoadhesive properties of the polymer. Taking cinaciguat as a hydrophobic model drug, drug nanocrystals were prepared by high pressure homogenization and then encapsulated in chitosan microparticles via spray drying. Through various in vitro characterizations, it was shown that drug loaded microparticles had a high drug loading with promising aerosolization characteristics (mean volume diameter (Dv50) 3–4μm, experimental mass mean aerodynamic diameter (MMADe) 4–4.5μm, fine particle fraction (FPF%) 40–45%, emitted dose (ED%) 94–95%). The microparticles showed high swelling capacity within 5min, with various sustained drug release rates depending on chitosan concentration and molecular weight. Furthermore, aerosolization performances under various inhalation conditions were investigated. It was found that both inspiratory flow rate and volume had an influence on the aerosolization of developed microparticles, indicating actual inhalation efficiency might be compromised under disease conditions. Taken together, in vitro data indicate that chitosan based swellable microparticles could potentially be useful as nanocrystal carrier to achieve sustained pulmonary delivery. To complete the feasibility assessment of this formulation principle, future in vivo safety and efficacy studies are needed.

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

Extrinsic lactose fines improve dry powder inhaler formulation performance of a cohesive batch of budesonide via agglomerate formation and consequential co-deposition

The aim of the study was to investigate how the fine particle content of lactose carriers prepared with different types of lactose fines regulates dry powder inhaler (DPI) formulation performance of a cohesive batch of micronised budesonide. Budesonide formulations (0.8wt%) were prepared with three different lactose carriers (Lactohale (LH) LH100, 20wt% LH210 in LH100 and 20wt% LH300 in LH100). Fine particle fraction of emitted dose (FPFED) and mean mass aerodynamic diameter (MMAD) of budesonide was assessed with a Next Generation Impactor (NGI) using a Cyclohaler at 90l/min. Morphological and chemical characteristics of particles deposited on Stage 2 were determined using a Malvern Morphologi G3-ID. The results indicate that increasing concentration of lactose fines (<4.5μm) not only increased the FPFED but also the MMAD of budesonide, suggesting drug deposition in agglomerates. Presence of agglomerates on Stage 2 was confirmed by morphological analysis of particles. Raman analysis of material collected on Stage 2 indicated that the more fine lactose particles were available the more agglomerates of budesonide and lactose were delivered to Stage 2. These results suggest drug-fines agglomerate formation is an important mechanism for how lactose fines improve and regulate DPI formulation performance.

One-year observations of size distribution characteristics of major aerosol constituents at a coastal receptor site in Hong Kong – Part 1: Inorganic ions and oxalate

Abstract. Size distribution data of major aerosol constituents are essential in source apportioning of visibility degradation, testing and verification of air quality models incorporating aerosols. We report here 1-year observations of mass size distributions of major inorganic ions (sulfate, nitrate, chloride, ammonium, sodium, potassium, magnesium and calcium) and oxalate at a coastal suburban receptor site in Hong Kong, China. A total of 43 sets of size-segregated samples in the size range of 0.056–18 μm were collected from March 2011 to February 2012. The size distributions of sulfate, ammonium, potassium and oxalate were characterized by a dominant droplet mode with a mass mean aerodynamic diameter (MMAD) in the range of ~ 0.7–0.9 μm. Oxalate had a slightly larger MMAD than sulfate on days with temperatures above 22 °C as a result of the process of volatilization and repartitioning. Nitrate was mostly dominated by the coarse mode but enhanced presence in fine mode was detected on winter days with lower temperature and lower concentrations of sea salt and soil particles. This data set reveals an inversely proportional relationship between the fraction of nitrate in the fine mode and product of the sum of sodium and calcium in equivalent concentrations and the dissociation constant of ammonium nitrate (i.e., (1/([Na+] + 2[Ca2+]) × (1/Ke')) when Pn_fine is significant (&gt; 10%). The seasonal variation observed for sea salt aerosol abundance, with lower values in summer and winter, is possibly linked with the lower marine salinities in these two seasons. Positive matrix factorization was applied to estimate the relative contributions of local formation and transport to the observed ambient sulfate level through the use of the combined data sets of size-segregated sulfate and select gaseous air pollutants. On average, the regional/super-regional transport of air pollutants was the dominant source at this receptor site, especially on high-sulfate days while local formation processes contributed approximately 30% of the total sulfate. This work provides field-measurement-based evidence important for understanding both local photochemistry and regional/super-regional transport in order to properly simulate sulfate aerosols in air quality models.

Improvement of the dispersibility of spray-dried budesonide powders using leucine in an ethanol–water cosolvent system

Abstract A new approach for enhancing the dispersibility of respirable powders containing poorly soluble pharmaceutical actives is demonstrated. Budesonide was spray-dried with leucine from an ethanol–water cosolvent feedstock. For near-azeotropic cosolvent ratios, leucine was enriched on the surface of the particles relative to the bulk composition, and the particles showed a low-density morphology. Partial encapsulation of budesonide was accomplished. The dispersibility and manufacturability of the powder were greatly improved relative to powders made from budesonide alone. Fine particle fractions from a passive dry powder inhaler exceeded 80%. The particle size was in a suitable range for respiratory drug delivery (mass mean aerodynamic diameter between 2 and 3 μm). These results demonstrate that leucine can be used in ethanol–water cosolvent systems to design respirable particles with high dispersibility and good manufacturability.

Reverse aqueous microemulsions in hydrofluoroalkane propellants and their aerosol characteristics

In this work we describe the structure and environment of reverse aqueous microemulsions formed in 1,1,1,2-tetrafluoroethane (HFA134a) propellant in the presence of a non-ionic ethoxylated copolymer, and the aerosol characteristics of the corresponding pressurized metered dose inhaler (pMDI) formulations. The activity of selected polypropylene oxide–polyethylene oxide–polypropylene oxide (PO m EO n PO m ) amphiphiles at the HFA134a–water interface was studied using in situ high-pressure tensiometry, and those results were used as a guide in the selection of the most appropriate candidate surfactant for the formation of microemulsions in the compressed HFA134a. The environment and structure of the aggregates formed with the selected surfactant candidate, PO 22EO 14PO 22, was probed via UV–vis spectroscopy (molecular probe), and small angle neutron scattering (SANS), respectively. High water loading capacity in the core of the nanoaggregates was achieved in the presence of ethanol. At a water-to-surfactant molar ratio of 21 and 10% ethanol, cylindrical aggregates with a radius of 18 Å, and length of 254 Å were confirmed with SANS. Anderson Cascade Impactor (ACI) results reveal that the concentration of the excipients ( C exp, including surfactant, water and ethanol) has a strong effect on the aerosol characteristics of the formulations, including the respirable fraction, and the mass mean aerodynamic diameter (MMAD), and that the trend in MMAD can be predicted as a function of the C exp following similar correlations to those proposed to common non-volatile excipients, indicating that the nanodroplets of water dispersed in the propellant behave similarly to molecularly solubilized compounds. Cytotoxicity studies of PO 22EO 14PO 22 were performed in A549 cells, an alveolar type II epithelial cell line, and indicate that, within the concentration range of interest, the surfactant in question decreases cell viability only lightly. The relevance of this work stems from the fact that aqueous-based HFA-pMDIs are expected to be versatile formulations, with the ability to carry a range of medically relevant hydrophilic compounds within the nanocontainers, including high potency drugs, drug combinations and biomacromolecules.