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1.
AAPS PharmSciTech ; 20(7): 271, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363868

RESUMO

Dry powder inhalers have attracted more interest over the years in every aspect related to them. Interestingly, when focusing on the effects of particle morphology of the active or carrier (excipient), it is generally regarded particle size and shape to influence drug availability of aerosolized particles. However, to date, few studies have examined the effect of texture, i.e., roughness, on this relationship. The main objective of the present work is to gain a closer understanding of the influence of carrier morphology on the aerosolization performance of dry powder inhaler formulations. Image analysis and microscopy were used to visualize the aerosolization process. It is considered that the scale of morphological features on the surface of the carrier particles is responsible for the dispersion of the powder formulation, separation of the drug/carrier, and entrainment from a dry powder inhaler. Thus, for this study, the carrier particles of different surface roughness were mixed with micronized salbutamol sulphate. Aerosolization in vitro testing was used to evaluate the performance. The results indicate a connection between the qualitative surface roughness of coarse carriers and aerosolization performance during powder dispersibility. This investigation demonstrated that indeed, powder dispersion, a dynamic process, is influenced by the scale of the carrier morphology.


Assuntos
Albuterol/química , Albuterol/farmacocinética , Broncodilatadores/química , Broncodilatadores/farmacocinética , Química Farmacêutica/métodos , Inaladores de Pó Seco/métodos , Administração por Inalação , Aerossóis/química , Aerossóis/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Inaladores de Pó Seco/instrumentação , Excipientes/química , Excipientes/farmacocinética , Tamanho da Partícula , Pós , Propriedades de Superfície
3.
AAPS PharmSciTech ; 20(5): 206, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147791

RESUMO

The multi-stage cascade impactor (CI) is the mainstay method for the determination of the aerodynamic particle size distribution (APSD) of aerosols emitted from orally inhaled products (OIPs). CIs are designed to operate at a constant flow rate throughout the measurement process. However, it is necessary to mimic an inhalation maneuver to disperse the powder into an aerosol when testing passive dry powder inhalers (DPIs), which constitute a significant portion of available products in this inhaler class. Methods in the pharmacopeial compendia intended for product quality assurance initiate sampling by applying a vacuum to the measurement apparatus using a timer-operated solenoid valve located downstream of the CI, resulting in a period when the flow rate through the impactor rapidly increases from zero towards the target flow rate. This article provides recommendations for achieving consistent APSD measurements, including selection of the CI, pre-separator, and flow control equipment, as well as reviewing considerations that relate to the shape of the flow rate-sampling time profile. Evidence from comparisons of different DPIs delivering the same active pharmaceutical ingredients (APIs) is indicative that the compendial method for APSD measurement is insensitive as a predictor of pharmacokinetic outcomes. Although inappropriate for product quality testing, guidance is therefore provided towards adopting a more clinically realistic methodology, including the use of an anatomically appropriate inlet and mimicking patient inhalation at the DPI while operating the CI at constant flow rate. Many of these recommendations are applicable to the testing of other OIP classes.


Assuntos
Aerossóis/normas , Inaladores de Pó Seco/métodos , Desenho de Equipamento/métodos , Tamanho da Partícula , Controle de Qualidade , Administração por Inalação , Aerossóis/administração & dosagem , Aerossóis/química , Inaladores de Pó Seco/instrumentação , Desenho de Equipamento/instrumentação , Humanos , Pós , Fármacos do Sistema Respiratório/administração & dosagem , Fármacos do Sistema Respiratório/química , Fármacos do Sistema Respiratório/normas , Tecnologia Farmacêutica/métodos
4.
Chemosphere ; 231: 478-486, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31151007

RESUMO

Secondary organic aerosol (SOA) is a complex mixture consisting of a variety of oxidation products. In this study, the role of relative humidity (RH) on SOA formation with different [H2O2]0/[cyclohexene]0 was investigated in a smog chamber. It was found that the cyclohexene SOA yield increases with increasing initial OH concentration at both high and low RH conditions. The increased rate of SOA formation was lower at wet conditions than that at dry conditions. For [H2O2]0/[cyclohexene]0 = 0.4 and 0.8, the SOA yield increased from 1.5% to 8% at dry condition to 7% and 12% at wet condition, respectively. In contrast, at high RH the SOA yield fell from 54% to 52% for [H2O2]0/[cyclohexene]0 = 1.3. The SOA mass loss was higher at high RH at the same OH exposure. The chemical composition of SOA was characterized using hybrid quadrupole-orbitrap mass spectrometer equipped with electrospray ionization (ESI-Q-Orbitrap-HRMS). Oligomers, which were responsible for the increase of the SOA yield, were detected in the SOA formed at high RH conditions. The esterification reaction between dicarboxylic acids and HOC6H10-O-O-C6H10OH was the pathway of oligomers formation. All the oligomers have cyclic molecular structures. For [H2O2]0/[cyclohexene]0 = 1.3, the relative intensity of both low and high molecular weight substances reduced more at wet conditions. This indicates that at sufficient OH level, the inhibition of oligomers formation and the further reaction of SOA with OH result in a slightly lower SOA yield at wet condition.


Assuntos
Aerossóis/química , Poluentes Atmosféricos/química , Cicloexenos/química , Umidade , Peróxido de Hidrogênio , Modelos Químicos , Estrutura Molecular , Oxirredução , Ozônio/química , Processos Fotoquímicos
5.
Chem Biol Interact ; 309: 108712, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31201777

RESUMO

The recent intentional use of nerve agents and pesticides in Europe and Afghanistan highlights the need for an effective countermeasure against organophosphates (OP) toxins. The most developed pretreatment candidate to date is plasma (native) human butyrylcholinesterase (HuBChE), which is limited in availability and because of its 1:1 stoichiometry with OPs, a large dose will present challenges when delivered parenterally both in terms of pharmacokinetics and manageability in the field. A tetrameric recombinant (r) form of human BChE produced in CHO-K1 cells with similar structure, in vivo stability and antidotal efficacy as the native form, has been developed to deliver rHuBChE as an aerosol (aer) to form a pulmonary bioshield capable of neutralizing inhaled OPs in situ and prevent AChE inhibition in the blood and in the brain; the latter associated with the symptoms of OP toxicity. Previous proof-of-concept macaque studies demonstrated that delivery of 9 mg/kg using a microsprayer inserted down the trachea, resulted in protection against an inhaled dose of 15ug/kg of aer-paraoxon (aer-Px) given 72 h later. In the present studies, pulmonary delivery of rHuBChE in macaques was achieved using Aerogen vibrating mesh nebulizers, similar to that used for human self-administration. The promising findings indicate that despite the poor lung deposition observed in macaques using nebulizers (13-20%), protective levels of RBC-AChE were still present in the blood even when exposure aer-Px (55 µg/kg) was delayed for five days. This long term retention of 5 mg/kg rHuBChE deposited in the lung bodes well for the use of an aer-rHuBChE pretreatment in humans where a user-friendly customized nebulizer with increased lung deposition up to 50% will provide even longer protection at a lower dose.


Assuntos
Aerossóis/química , Butirilcolinesterase/química , Paraoxon/química , Animais , Butirilcolinesterase/genética , Butirilcolinesterase/metabolismo , Células CHO , Cricetinae , Cricetulus , Feminino , Humanos , Pulmão/metabolismo , Macaca , Masculino , Nebulizadores e Vaporizadores , Paraoxon/toxicidade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/sangue , Proteínas Recombinantes/química
6.
Pharm Res ; 36(8): 110, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31139939

RESUMO

PURPOSE: To determine the predictive power of computational fluid dynamics (CFD)-based dispersion parameters in the development of a new inline DPI that is actuated with low volumes of air. METHODS: Four new versions of a dose aerosolization and containment (DAC)-unit DPI were created with varying inlet and outlet orifice sizes and analyzed with results from five previous designs. A concurrent in vitro and CFD analysis was conducted to predict the emitted dose (ED; as a % of loaded dose) and aerosol mass median aerodynamic diameter (MMAD) produced by each device when actuated with 10 ml air bursts. CFD simulations of device operation were used to predict flow field and particle-based dispersion parameters. RESULTS: Comparisons of experimental and CFD results indicated that multiple flow field and particle-based dispersion parameters could be used to predict ED (minimum RMS Error = 4.9%) and MMAD (minimum RMS Error = 0.04 µm) to a high degree of accuracy. Based on experiments, the best overall device produced mean (standard deviation; SD) ED = 82.9(4.3)% and mean MMAD (SD) = 1.73(0.07)µm, which were in close agreement with the CFD predictions. CONCLUSIONS: A unique relationship was identified in the DAC-unit DPI in which reducing turbulence also reduced the MMAD.


Assuntos
Simulação por Computador , Inaladores de Pó Seco/instrumentação , Hidrodinâmica , Administração por Inalação , Aerossóis/química , Ar , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/instrumentação , Desenho de Equipamento/instrumentação , Humanos , Modelos Biológicos , Tamanho da Partícula , Pós/administração & dosagem
7.
Chemosphere ; 231: 276-286, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129409

RESUMO

The formation of secondary organic aerosol (SOA) generated by irradiating styrene in the presence and/or absence of OH, NOx, H2O vapour and seed aerosol has been investigated for the first time. Experiments were conducted in a smog chamber at 298 K and atmospheric pressure. Styrene decay was measured by gas chromatography with a mass spectrometric detector (GC-MS), and the temporal evolution of the aerosol was monitored using a fast mobility particle sizer (FMPS). The SOA yield increases as the initial styrene concentration increases, leading to yields ranging from 1.8% to 3.5% for styrene photolysis, and from 2.4% to 5.0% for its photooxidation. In both cases, the organic aerosol formation can be expressed by a one-product gas/particle partitioning absorption model. The particle number concentration, mass and yield decrease in the presence of NOx and seed aerosol but increase at higher relative humidity (RH). The gas phase and SOA composition were analysed offline using a filter/denuder sampling system simultaneously collecting gas- and particle-phase products. Benzaldehyde was confirmed as the main gas-phase product of the reaction. However, although products in the particle phase were detected, they could not be identified. Moreover, the aqueous filter extracts were analysed using UV-Visible spectrophotometry to determine differences in the optical properties of SOA produced in the presence and absence of NOx. The results from this work may be used to discuss the implications of atmospheric SOA generation from styrene degradation.


Assuntos
Aerossóis/química , Radical Hidroxila/química , Estireno/química , Gases , Modelos Químicos , Processos Fotoquímicos , Fotólise , Água
8.
Environ Pollut ; 251: 442-452, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103004

RESUMO

Severe pollution caused by atmospheric particulate matter (PM) has become a global environmental issue. Samples of atmospheric PM were collected before and during the Chinese Spring Festival in Xiamen, a coastal city in Southeast China, to investigate their chemical characteristics, sources, and formation mechanisms. The results indicated that PM2.5 mass concentrations comprised 53.60% and 56.31% of total suspended particulates before and during the Spring Festival, respectively. Due to the halt of factory production and construction and the reduction of vehicle flow during the Spring Festival, the concentrations of organic carbon, elemental carbon and water soluble ions in PM2.5 decreased by 78.56%, 84.19% and 27.53%, respectively, compared with those before the Spring Festival. However, the concentrations of K+, Mg2+, Al, Sr, and Ba increased by 3121.76%, 571.67%, 183.71%, 180.15%, and 137.58%, respectively, resulting from the display of fireworks and firecrackers during the Spring Festival. Analysis of backward air mass trajectory indicated that the concentrations of PM2.5 and its components were dominated by local pollution sources before and during the Spring Festival. The relationships between meteorological conditions and pollutant concentrations showed that the secondary organic aerosol was generated from the heterogeneous reaction before the Spring Festival, and the secondary inorganic aerosol was formed by the photochemical reaction during the Spring Festival.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Aerossóis/química , Poluentes Atmosféricos/química , Carbono/análise , China , Cidades , Monitoramento Ambiental , Férias e Feriados , Íons/análise , Tamanho da Partícula , Material Particulado/química
9.
J Chromatogr A ; 1599: 85-94, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30961966

RESUMO

Polysialic acid (polySia) is widely investigated in various biopharmaceutical applications (e.g. treatment of inflammatory neurodegenerative diseases), whereby a certain polySia chain length with an average degree of polymerization 20 (polySia avDP20) shows most promising effects. In this study, a rapid analytical method using a HPLC and charged aerosol detector (CAD) for the direct chain length characterization of biopharmaceutically relevant polySia was developed. It was evaluated as a fast alternative to the commonly used 1,2-diamino-4,5-methylenedioxybenzene (DMB) HPLC application. In contrast to HPLC-FLD, the CAD-application provides the actual chain length of polySia within ∼3 h. The reliability of the HPLC-CAD was evaluated with a commercial reference sample of known chain length and biotechnologically produced LC polySia (long chain polySia with a DP ∼130). Moreover, HPLC-CAD was successfully applied in the direct detection of oligo- and polySia until DP ∼65 and can be used to monitor the thermal hydrolysis and subsequent chromatographic isolation of polySia avDP20 (average degree of polymerization 20) without DMB sample derivatization. In addition, CAD was successfully applied for polySia quantification using a modified elution gradient. It was tested as a fast alternative to commonly used thiobarbituric acid (TBA) assay. A differentiation between LC polySia and smaller, hydrolysed polySia chains was intended and possible. For LC polySia and polySia avDP20, a quadratic relation between polySia mass-concentration and CAD signal was observed. In case of LC polySia, a quadratic dependency with a determination coefficient of R2 = 0.99 in a broad concentration range between 0.025 and 15 mg mL-1 was determined. Quantification of polySia avDP20 was found to have quadratic dependency with a determination coefficient of R2 = 0.99 in a concentration range between 0.02 and 0.25 mg mL-1. The HPLC-CAD was tested for quantification with polySia references of known concentration and showed high accordance with a concentration deviation ≤6.7%. The CAD quantification method was also applied in the polySia avDP20 production process and was compared to the TBA assay. Results of a correlation plot showed a high determination coefficient of R2 = 0.98. Overall, HPLC-CAD analysis was successfully tested as a suitable characterization and quantification application in the biopharmaceutical production of polySia.


Assuntos
Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão , Escherichia coli/química , Ácidos Siálicos/análise , Aerossóis/química , Hidrólise , Polimerização , Reprodutibilidade dos Testes
10.
Environ Pollut ; 250: 627-638, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31035145

RESUMO

The study of aerosol dispersion characteristics in wastewater treatment plants (WWTPs) has attracted extensive attention. Oxidation ditch (OD) is a commonly implemented process during biological wastewater treatment. This study assessed the component characteristics, source apportionment, and exposure risks of aerosols generated from a WWTP using the OD process (AWO). The results indicated that the aeration part of oxidation ditch (ODA) exhibited the highest concentrations and proportions of the respiratory fractions (RF) of bacteria, Enterobacteriaceae, Staphylococcus aureus, and Pseudomonas aeruginosa. Some pathogenic or opportunistic-pathogenic bacteria and carcinogenic metal(loid)s were detected in the AWO. The source apportionment results indicated that the outdoor wastewater treatment processes and ambient air contributed to the constitution of the AWO. The indoor aerosols were mainly constituted by composition of the wastewater treatment process such as the sludge dewatering room (SDR). The pathogenic or opportunistic-pathogenic bacteria with eight genera (Colinsella, Dermatophilus, Enterobactor, Erycherichia-Shigella, Ledionella, Selenomonas, Xanthobacter, and Veillonella) were largely attributed to wastewater or sludge. The risk assessment suggested that inhalation was the main exposure pathway for aerosols (including bacteria and metal(loid)s). Additionally, As indicated the highest non-carcinogenic risks. Furthermore, As, Cd, and Co were associated with high carcinogenic risks. The ODA and sludge dewatering room (SDR) indicated the highest carcinogenic and non-carcinogenic risks of metal(loid)s, respectively. Thus, the AWO should be sufficiently researched and monitored to mitigate their harmful effects on human health, particularly with regard to the health of the site workers.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Águas Residuárias/química , Purificação da Água , Aerossóis/química , Aerossóis/toxicidade , Poluentes Atmosféricos/química , Poluentes Atmosféricos/toxicidade , Bactérias/classificação , Bactérias/isolamento & purificação , China , Humanos , Oxirredução , Tamanho da Partícula , Medição de Risco , Esgotos/microbiologia , Águas Residuárias/microbiologia
11.
J Chromatogr A ; 1599: 247-252, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31030953

RESUMO

Thermal desorption aerosol gas chromatography (TAG) is an effective tool for in situ analysis of particulate organic molecules. However, the performance of current TAG is limited by the detectability of low volatile compounds and the matrix effect. In this study, a dual-trap TAG system was developed to address these issues. Thermally desorbed effluent is focused by a weakly retained trap (for low volatile compounds) in a 1 m capillary column conditioned in the GC oven, followed by a strongly retained trap (for high volatile compounds). Then, the focused analytes are desorbed in a reverse flow into the GC column for analysis. Detection over a wide volatility range from C10 to C40 n-alkanes is achieved using the dual-trap TAG. We show that it has lower discrimination of injection, better linearity and higher detectability of n-alkanes. The dual-trap TAG was applied for in-situ measurement of ambient fine particles (PM2.5) in Beijing. Repeatable retention time of n-alkanes was demonstrated during a continuous measurement over two weeks.


Assuntos
Cromatografia Gasosa/instrumentação , Monitoramento Ambiental/métodos , Aerossóis/química , Alcanos/análise , Pequim , Temperatura Alta , Material Particulado/análise , Volatilização
12.
Respir Res ; 20(1): 66, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943978

RESUMO

BACKGROUND: Interferon gamma (IFN-γ) is a clinically relevant immunomodulatory cytokine that has demonstrated significant potential in the treatment and management of respiratory diseases such as tuberculosis and pulmonary fibrosis. As with all large biomolecules, clinical translation is dependent on effective delivery to the disease site and delivery of IFN-γ as an aerosol offers a logical means of drug targeting. Effective localization is often hampered by instability and a lack of safe and efficient delivery systems. The present study sought to determine how effectively IFN-γ can be nebulized using two types of vibrating mesh nebulizer, each with differing mesh architectures, and to investigate the comparative efficiency of delivery of therapeutically active IFN-γ to the lungs. METHODS: Nebulization of IFN-γ was carried out using two different Aerogen vibrating mesh technologies with differing mesh architectures. These technologies represent both a standard commercially available mesh type (Aerogen Solo®) and a new iteration mesh (Photo-defined aperture plate (PDAP®). Extensive aerosol studies (aerosol output and droplet analysis, non-invasive and invasive aerosol therapy) were conducted in line with regulatory requirements and characterization of the stability and bioactivity of the IFN-γ post-nebulization was confirmed using SDS-PAGE and stimulation of Human C-X-C motif chemokine 10 (CXCL 10) also known as IFN-γ-induced protein 10KDa (IP 10) expression from THP-1 derived macrophages (THP-1 cells). RESULTS: Aerosol characterization studies indicated that a significant and reproducible dose of aerosolized IFN-γ can be delivered using both vibrating mesh technologies. Nebulization using both devices resulted in an emitted dose of at least 93% (100% dose minus residual volume) for IFN-γ. Characterization of aerosolized IFN-γ indicated that the PDAP was capable of generating droplets with a significantly lower mass median aerodynamic diameter (MMAD) with values of 2.79 ± 0.29 µm and 4.39 ± 0.25 µm for the PDAP and Solo respectively. The volume median diameters (VMD) of aerosolized IFN-γ corroborated this with VMDs of 2.33 ± 0.02 µm for the PDAP and 4.30 ± 0.02 µm for the Solo. SDS-PAGE gels indicated that IFN-γ remains stable after nebulization by both devices and this was confirmed by bioactivity studies using a THP-1 cell model in which an alveolar macrophage response to IFN-γ was determined. IFN-γ nebulized by the PDAP and Solo devices had no significant effect on the key inflammatory biomarker cytokine IP-10 release from this model in comparison to non-nebulized controls. Here we demonstrate that it is possible to combine IFN-γ with vibrating mesh nebulizer devices and facilitate effective aerosolisation with minimal impact on IFN-γ structure or bioactivity. CONCLUSIONS: It is possible to nebulize IFN-γ effectively with vibrating mesh nebulizer devices without compromising its stability. The PDAP allows for generation of IFN-γ aerosols with improved aerodynamic properties thereby increasing its potential efficiency for lower respiratory tract deposition over current technology, whilst maintaining the integrity and bioactivity of IFN-γ. This delivery modality therefore offers a rational means of facilitating the clinical translation of inhaled IFN-γ.


Assuntos
Broncodilatadores/administração & dosagem , Interferon gama/administração & dosagem , Nebulizadores e Vaporizadores , Telas Cirúrgicas , Tecnologia Farmacêutica/instrumentação , Vibração , Administração por Inalação , Aerossóis/administração & dosagem , Aerossóis/química , Broncodilatadores/química , Humanos , Interferon gama/química , Tecnologia Farmacêutica/métodos , Vibração/uso terapêutico
13.
Macromol Rapid Commun ; 40(9): e1800832, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30892757

RESUMO

Recently, many researchers have developed advanced energy storage and energy conversion systems to address the increased demand for energy resources. The performance of these electrochemical energy storage and conversion devices depends considerably on the properties of their unique electrode materials. Among electrode materials, graphene (GR) has attracted much attention due to its unique properties of high flexibility, a large specific surface area, and superior electric conductivity rates that are well-suited to energy storage systems. Specifically, aerosol-made 3D GR composites are known to be more resistant to compressive forces such as paper balls owing to their stronger and harder compressive tolerance levels and higher and more stable surface areas compared to 2D GR sheets. These unique properties of 3D GR composites result in enhanced electrochemical performances for energy storage systems. This review focuses on recent studies of aerosol-made 3D GR-based composites for energy storage systems such as supercapacitors, lithium-ion batteries, and sodium-ion batteries.


Assuntos
Aerossóis/química , Fontes de Energia Elétrica , Grafite/química , Nanocompostos/química , Técnicas Eletroquímicas/métodos , Eletroquímica/métodos , Lítio/química
14.
AAPS PharmSciTech ; 20(3): 103, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30734187

RESUMO

Over the past 20 years, solution-based spray dried powders have transformed inhaled product development, enabling aerosol delivery of a wider variety of molecules as dry powders. These include inhaled proteins for systemic action (e.g., Exubera®) and high-dose inhaled antibiotics (e.g., TOBI® Podhaler™). Although engineered particles provide several key advantages over traditional powder processing technologies (e.g., spheronized particles and lactose blends), the physicochemical stability of the amorphous drug present in these formulations brings along its own unique set of constraints. To this end, a number of approaches have been developed to maintain the crystallinity of drugs throughout the spray drying process. One approach is to spray dry suspensions of micronized drug(s) from a liquid feed. In this method, minimization of drug particle dissolution in the liquid feed is critical, as dissolved drug is converted into amorphous domains in the spray-dried drug product. The review explores multiple formulation and engineering strategies for decreasing drug dissolution independent of the physicochemical properties of the drug(s). Strategies to minimize particle dissolution include spray blending of particles of different compositions, formation of respirable agglomerates of micronized drug with small porous carrier particles, and use of common ions. The formulations extend the range of doses that can be delivered with a portable inhaler from about 100 ng to 100 mg. The spray-dried particles exhibit significant advantages in terms of lung targeting and dose consistency relative to conventional lactose blends, while still maintaining the crystallinity of drug(s) in the formulated drug product.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/química , Inaladores de Pó Seco/métodos , Tamanho da Partícula , Administração por Inalação , Aerossóis/administração & dosagem , Aerossóis/química , Aerossóis/farmacocinética , Animais , Antibacterianos/farmacocinética , Cristalização/métodos , Dessecação , Humanos , Lactose/administração & dosagem , Lactose/química , Lactose/farmacocinética , Nebulizadores e Vaporizadores , Pós
15.
J Environ Sci (China) ; 79: 256-263, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30784449

RESUMO

Current atmospheric quality models usually underestimate the level of ambient secondary organic aerosol (SOA), one of the possible reasons is that the precursors at different concentrations may undergo different oxidation processes and further affect SOA formation. Therefore, there is a need to perform more chamber studies to disclose the influence. In this work, SOA formation over a wide range of initial precursor concentrations (tens of ppb to hundreds of ppb levels) was investigated in a 30 m3 indoor smog chamber, and mainly through the analysis of multiple generations of VOCs detected from HR-ToF-PTRMS to expound the difference in the oxidation process between low and high precursor concentrations. Compared to high initial concentrations, gas-phase intermediates formed at low concentrations had a higher intensity by about one order of magnitude, and the low-volatility compounds also had a higher formation potential due to the competition between semi-volatile intermediates and precursors with oxidants. In addition, the formed SOA was more oxidized with higher f44 value (0.14 ±â€¯0.02) and more relevant to real atmosphere than that formed at high concentrations. This work should help to deeply understand SOA formation and improve the performance of air quality models for SOA simulation.


Assuntos
Aerossóis/química , Poluentes Atmosféricos/química , Óxidos de Nitrogênio/química , Smog , Compostos Orgânicos Voláteis/química , Poluição do Ar , Derivados de Benzeno/química , Oxirredução
16.
Int J Pharm ; 561: 102-113, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30797863

RESUMO

Combinational antibiotic formulations have emerged as an important strategy to combat antibiotic resistance. The main objective of this study was to examine effects of individual components on the antimicrobial activity, physico-chemical properties, aerosolization and dissolution of powder aerosol formulations when three synergistic drugs were co-spray dried. A ternary dry powder formulation consisting of meropenem (75.5 %w/w), colistin (15.1 %w/w) and rifampicin (9.4 %w/w) at the selected ratio was produced by spray drying. The ternary formulation was characterized for in-vitro antibacterial activity, physico-chemical properties, surface composition, aerosol performance and dissolution. All of the formulations demonstrated excellent aerosolization behavior achieving a fine particle fraction of >70%, which was substantially higher than those for the Meropenem-SD and Colistin-Meropenem formulations. The results indicated that rifampicin controlled the surface morphology of the ternary and binary combination formulations resulting in the formation of highly corrugated particles. Advanced characterization of surface composition by XPS supported the hypothesis that rifampicin was enriched on the surface of the combination powder formulations. All spray-dried formulations were amorphous and absorbed substantial amount of water at the elevated humidity. Storage at the elevated humidity caused a substantial decline in aerosolization performance for the Meropenem-SD and Colistin-Meropenem, which was attributed to increased inter-particulate capillary forces or particle fusion. In contrast, the ternary combination and binary Meropenem-Rifampicin formulations showed no change in aerosol performance at the elevated storage humidity conditions; attributable to the enriched hydrophobicity of rifampicin on the particle surface that acted as a barrier against moisture condensation and particle fusion. Interestingly, in the ternary formulation rifampicin enrichment on the surface did not interfere with the dissolution of other two components (i.e. meropenem and colistin). Our study provides an insight on the impact of each component on the performance of co-spray dried combinational formulations.


Assuntos
Aerossóis/química , Colistina/química , Combinação de Medicamentos , Liberação Controlada de Fármacos , Meropeném/química , Pós/química , Rifampina/química , Aerossóis/farmacologia , Antibacterianos/química , Fenômenos Químicos , Colistina/farmacologia , Dessecação/métodos , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Pós/farmacologia , Rifampina/farmacologia , Propriedades de Superfície
17.
Environ Monit Assess ; 191(2): 78, 2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30649631

RESUMO

Aerosol particles play important roles in processes controlling the composition of the atmosphere and function of ecosystems. A better understanding of the composition of aerosol particles is beginning to be recognized as critical for ecological research to further comprehend the link between aerosols and ecosystems. While chemical characterization of aerosols has been practiced in the atmospheric science community, detailed methodology tailored to the needs of ecological research does not exist yet. In this study, we describe an efficient methodology (atmo-ecometabolomics), in step-by-step details, from the sampling to the data analyses, to characterize the chemical composition of aerosol particles, namely atmo-metabolome. This method employs mass spectrometry platforms such as liquid and gas chromatography mass spectrometries (MS) and Fourier transform ion cyclotron resonance MS (FT-ICR-MS). For methodology evaluation, we analyzed aerosol particles collected during two different seasons (spring and summer) in a low-biological-activity ecosystem. Additionally, to further validate our methodology, we analyzed aerosol particles collected in a more biologically active ecosystem during the pollination peaks of three different representative tree species. Our statistical results showed that our sampling and extraction methods are suitable for characterizing the atmo-ecometabolomes in these two distinct ecosystems with any of the analytical platforms. Datasets obtained from each mass spectrometry instrument showed overall significant differences of the atmo-ecometabolomes between spring and summer as well as between the three pollination peak periods. Furthermore, we have identified several metabolites that can be attributed to pollen and other plant-related aerosol particles. We additionally provide a basic guide of the potential use ecometabolomic techniques on different mass spectrometry platforms to accurately analyze the atmo-ecometabolomes for ecological studies. Our method represents an advanced novel approach for future studies in the impact of aerosol particle chemical compositions on ecosystem structure and function and biogeochemistry.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Atmosfera/química , Monitoramento Ambiental/métodos , Aerossóis/química , Poluentes Atmosféricos/química , Cromatografia Líquida , Ecossistema , Análise de Fourier , Cromatografia Gasosa-Espectrometria de Massas , Projetos de Pesquisa , Estações do Ano
18.
Int J Pharm ; 559: 68-75, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30677482

RESUMO

Meloxicam is an anti-inflammatory drug that could be interesting to deliver locally to the lungs to treat inflammation occurring in cystic fibrosis or chronic obstructive pulmonary disease (COPD). Spray drying conditions were optimized to prepare inhalable dry powders, from meloxicam aqueous solution with pH adjustment. A comparison study between non-porous and large porous particles (LPPs) was carried out to demonstrate the relevance of the aimed large size (>5 µm) and low density (<0.2 mg/cm3) formulations. With the appropriate amount of porogen agent, ammonium bicarbonate, LPPs exhibited the same aerodynamic diameter and a higher deposited fraction than smaller but dense particles. The aerodynamic evaluation of LPPs showed that the fine particle fraction (FPF) reached up to 65.8%, while the emitted fraction (EF) reached 85.4%, both higher than for the non-porous particles. Stability tests demonstrated that, after 10 weeks of storage, no significant difference could be detected in the aerodynamic behaviour of the formulations. To the best of our knowledge this is the first time large porous particles, with enhanced aerodynamic properties, from an aqueous solution of meloxicam are reported.


Assuntos
Pulmão/efeitos dos fármacos , Meloxicam/administração & dosagem , Meloxicam/química , Administração por Inalação , Aerossóis/administração & dosagem , Aerossóis/química , Química Farmacêutica/métodos , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Inaladores de Pó Seco/métodos , Tamanho da Partícula , Porosidade , Pós/administração & dosagem , Pós/química
19.
Chemosphere ; 215: 413-421, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30336318

RESUMO

TSP and 9-stage size-segregated samples were simultaneously collected in Xi'an during the spring of 2013 and analyzed for organic aerosols (OA) on a molecular level. n-Alkanes were the dominant compound class during the whole campaign, followed by fatty acids. High molecular weight (HMW) n-alkanes and fatty acids dominated in the coarse mode particles (>1.1 µm) during the dust event, indicating they were mostly originated from surface soil and plants in the upwind regions. Low-volatile anthropogenic compounds such as benzo(e)pyrene (BeP) and bisphenol A (BPA) dominated in the fine mode particles during the whole campaign. In contrast, semi-volatile anthropogenic compounds such as phenanthrene (Phe) and di-n-butyl phthalates (DBP) showed a bimodal size distribution with a significant increase in the coarse mode during the dust event due to their vaporization from the fine mode particles and the subsequent adsorption on the dust surface. Secondary organic aerosols (SOA) in Xi'an during the dust storm period were predominantly enriched on the coarse particles, which can be ascribed to the adsorption and subsequent oxidation of gas-phase hydrophilic organics on the aqueous-phase of hygroscopic dust surface (e.g., mirabilite). Our work suggested an important role of multiphase reaction in evolution of aerosol chemistry during the dust long-range transport process.


Assuntos
Aerossóis/química , Poluentes Atmosféricos/análise , Poeira/análise , Monitoramento Ambiental/métodos , Estações do Ano , Aerossóis/análise , Poluentes Atmosféricos/química , Alcanos/análise , Alcanos/química , China , Ácidos Graxos/análise , Ácidos Graxos/química , Compostos Orgânicos/química , Tamanho da Partícula , Volatilização
20.
Chemosphere ; 215: 554-562, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30342400

RESUMO

The hygroscopicity of aerosols is dependent upon their chemical composition. When their chemical compositions are altered, the water content in aerosols often changes, which may further modify phase behaviour. However, the study of phase behaviour dependence on chemical reactions is still limited. In this work, internally mixed sodium pyruvate (SP)/ammonium sulfate (AS) droplets were studied using an in-situ ATR-FTIR spectrometer. FTIR spectral analysis showed that solid sodium sulfate (SS) formed during the dehydration process, indicating a chemical reaction between SP and AS. In addition, the water content decreased after a dehydration-hydration process despite organic salt (SS) to inorganic salt (AS) mole ratios (OIRs) During the second relative humidity (RH) cycle, the water content remained constant, however, the efflorescence relative humidity (ERH) was lower than that in the first dehydration. The crystal relative humidities (CRHs) of SS are 66.7-53.1%, 66.0-58.2%, 62.2-57.1% and 49.6-43.6% for OIRs of 3:1, 2:1, 1:1 and 1:3, respectively, suggesting the crystallization of SS was favoured by higher SP content. For 2:1 OIRs, the solid SS was the greatest and an excess of either SP or AS blocked the solid SS formation. At a constant 80% RH, depletion of reagents was ∼0.97, and water loss was ∼0.6 in ∼40 min. After 90 min, solid SS formed. The chemical reaction was faster than water loss; furthermore, water loss from the chemical reaction led to solid SS above the ERH of pure SS particles (∼75% RH). When the RH changed rapidly, the reaction was slow and solid SS decreased.


Assuntos
Aerossóis/química , Sulfato de Amônio/química , Piruvatos/química , Sulfatos/química , Cristalização , Umidade , Água/química , Molhabilidade
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