Changes in body water distribution during treatment with inhaled steroid in pre-school children

DEFF Research Database (Denmark)

Heitmann, B L; Anhøj, Jacob; Bisgaard, A M

2004-01-01

.i.d. delivered via Babyhaler, budesonide pressurized metered dose inhaler (pMDI) 200 microg b.i.d. delivered via Nebuchamber and placebo. Spacers were primed before use. In total, 40 children aged 1-3 years, with mild intermittent asthma were included. Twenty-five of the children completed all three treatments...... overall this effect was not statistically significant (0.1 growth during inhaled steroid treatment seems to partly reflect generalized changes...

New Delivery Systems and Propellants

Directory of Open Access Journals (Sweden)

Myrna Dolovich

1999-01-01

Full Text Available The removal of chlorofluorocarbon (CFC propellants from industrial and household products has been agreed to by over 165 countires of which more than 135 are developing countries. The timetable for this process is outlined in the Montreal Protocol on Substances that Deplete the Ozone Layer document and in several subsequent amendments. Pressured metered dose inhalers (pMDIs for medical use have been granted temporary exemptions until replacement formulations, providing the same medication via the same route, and with the same efficacy and safety profiles, are approved for human use. Hydrofluoroalkanes (HFAs are the alternative propellants for CFCs-12 and -114. Their potential for damage to the ozone layer is nonexistent, and while they are greenhouse gases, their global warming potential is a fraction (one-tenth of that of CFCs. Replacement formulations for almost all inhalant respiratory medications have been or are being produced and tested; in Canada, it is anticipated that the transition to these HFA or CFC-free pMDIs will be complete by the year 2005. Initially, an HFA pMDI was to be equivalent to the CFC pMDI being replaced, in terms of aerosol properties and effective clinical dose. However, this will not necessarily be the situation, particularly for some corticosteroid products. Currently, only one CFC-free formulation is available in Canada – Airomir, a HFA salbutamol pMDI. This paper discusses the in vitro aerosol characteristics, in vivo deposition and clinical data for several HFA pMDIs for which there are data available in the literature. Alternative delivery systems to the pMDI, namely, dry powder inhalers and nebulizers, are briefly reviewed.

Characterization of the spray velocities from a pressurized metered-dose inhaler.

Science.gov (United States)

Crosland, Brian Michael; Johnson, Matthew Ronald; Matida, Edgar Akio

2009-06-01

Pressurized metered dose inhalers (pMDIs) are widely used to deliver aerosolized medications to the lungs, most often to relieve the symptoms of asthma. Over the past decade, pMDIs have been modified in several ways to eliminate the use of chlorofluorocarbons in their manufacture while increasing efficacy. Numerical simulations are being used more frequently to predict the flow and deposition of particles at various locations, both inside the respiratory tract as well as in pMDIs and add-on devices. These simulations require detailed information about the spray generated by a pMDI to ensure the validity of their results. This paper presents detailed, spatially resolved velocity measurements of the spray emitted from salbutamol sulfate pMDIs obtained using optically triggered particle image velocimetry (PIV). Instantaneous planar velocity measurements were taken and ensemble-averaged at nine different times during the spray event ranging from 1.3 to 100 msec after a pneumatically controlled actuation. The mean spray velocities were shown to be bimodal in time, with two velocity peaks and velocity magnitudes found to be much lower than published data from instantaneous single point measurements. Planar velocity data at each time step were analyzed to produce prescriptive velocity profiles suitable for use in numerical simulations. Spray geometry data are also reported. Statistical comparisons from several thousand individual spray events indicate that there is no significant difference in measured velocity among (1) two brands of pMDI canisters, (2) two pMDIs of the same brand but having different lot numbers, and (3) a full pMDI versus an almost empty pMDI. The addition of a secondary air flow of 30 SLPM (to represent simultaneous inhalation and spray actuation) deflected the spray downward but did not have a significant effect on flow velocity. Further experiments with an added cylindrical spacer revealed that within the spacer, the spray direction and cone angle

Formulation and Development of Metered Dose Inhalations of Salbutamol in Solution Form

Science.gov (United States)

Khale, Anubha; Bajaj, Amrita

2011-01-01

In the present study attempts were made to prepare metered dose inhalation of salbutamol in solution form and compared it with the marketed metered dose inhalation in suspension form. Solution form of the drug was found better than marketed suspension formulation with respect to homogeneity and content uniformity. Propellant blend P-11 and P-12 in the proportion 30:70 was selected as it gave optimum vapour pressure. Surfactant oleic acid in concentration 10 mg per can was selected as it gave best results with clarity, spray pattern, vapour pressure, content per spray and rate of evaporation. Ethyl alcohol 2 ml per can was used as a cosolvent to give a clear solution, optimum vapour pressure, maximum content per spray and fair rate of evaporation. The selected formulation was subjected to the physico-chemical evaluation tests as per the standard pharmacopoeial procedures and the characteristics of the formulations were further compared with a conventional marketed formulation. In vitro study reveled the net respirable fraction was better than marketed preparation. PMID:22923867

[Development of Inhalable Dry Powder Formulations Loaded with Nanoparticles Maintaining Their Original Physical Properties and Functions].

Science.gov (United States)

Okuda, Tomoyuki

2017-01-01

 Functional nanoparticles, such as liposomes and polymeric micelles, are attractive drug delivery systems for solubilization, stabilization, sustained release, prolonged tissue retention, and tissue targeting of various encapsulated drugs. For their clinical application in therapy for pulmonary diseases, the development of dry powder inhalation (DPI) formulations is considered practical due to such advantages as: (1) it is noninvasive and can be directly delivered into the lungs; (2) there are few biocomponents in the lungs that interact with nanoparticles; and (3) it shows high storage stability in the solid state against aggregation or precipitation of nanoparticles in water. However, in order to produce effective nanoparticle-loaded dry powders for inhalation, it is essential to pursue an innovative and comprehensive formulation strategy in relation to composition and powderization which can achieve (1) the particle design of dry powders with physical properties suitable for pulmonary delivery through inhalation, and (2) the effective reconstitution of nanoparticles that will maintain their original physical properties and functions after dissolution of the powders. Spray-freeze drying (SFD) is a relatively new powderization technique combining atomization and lyophilization, which can easily produce highly porous dry powders from an aqueous sample solution. Previously, we advanced the optimization of components and process conditions for the production of SFD powders suitable to DPI application. This review describes our recent results in the development of novel DPI formulations effectively loaded with various nanoparticles (electrostatic nanocomplexes for gene therapy, liposomes, and self-assembled lipid nanoparticles), based on SFD.

Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers.

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Islam, Nazrul; Richard, Derek

2018-05-24

Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dry powder inhaler formulation of lipid-polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles.

Science.gov (United States)

Yang, Yue; Cheow, Wean Sin; Hadinoto, Kunn

2012-09-15

Lipid-polymer hybrid nanoparticles have emerged as promising nanoscale carriers of therapeutics as they combine the attractive characteristics of liposomes and polymers. Herein we develop dry powder inhaler (DPI) formulation of hybrid nanoparticles composed of poly(lactic-co-glycolic acid) and soybean lecithin as the polymer and lipid constituents, respectively. The hybrid nanoparticles are transformed into inhalable microscale nanocomposite structures by a novel technique based on electrostatically-driven adsorption of nanoparticles onto polysaccharide carrier particles, which eliminates the drawbacks of conventional techniques based on controlled drying (e.g. nanoparticle-specific formulation, low yield). First, we engineer polysaccharide carrier particles made up of chitosan cross-linked with tripolyphosphate and dextran sulphate to exhibit the desired aerosolization characteristics and physical robustness. Second, we investigate the effects of nanoparticle to carrier mass ratio and salt inclusion on the adsorption efficiency, in terms of the nanoparticle loading and yield, from which the optimal formulation is determined. Desorption of the nanoparticles from the carrier particles in phosphate buffer saline is also examined. Lastly, we characterize aerosolization efficiency of the nanocomposite product in vitro, where the emitted dose and respirable fraction are found to be comparable to the values of conventional DPI formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Development and comparison of new high-efficiency dry powder inhalers for carrier-free formulations.

Science.gov (United States)

Behara, Srinivas R B; Longest, P Worth; Farkas, Dale R; Hindle, Michael

2014-02-01

High-efficiency dry powder inhalers (DPIs) were developed and tested for use with carrier-free formulations across a range of different inhalation flow rates. Performance of a previously reported DPI was compared with two new designs in terms of emitted dose (ED) and aerosolization characteristics using in vitro experiments. The two new designs oriented the capsule chamber (CC) at different angles to the main flow passage, which contained a three-dimensional (3D) rod array for aerosol deaggregation. Computational fluid dynamics simulations of a previously developed deaggregation parameter, the nondimensional specific dissipation (NDSD), were used to explain device performance. Orienting the CC at 90° to the mouthpiece, the CC90 -3D inhaler provided the best performance with an ED = 73.4%, fine particle fractions (FPFs) less than 5 and 1 μm of 95.1% and 31.4%, respectively, and a mass median aerodynamic diameter (MMAD) = 1.5 μm. For the carrier-free formulation, deaggregation was primarily influenced by capsule aperture position and the NDSD parameter. The new CC-3D inhalers reduced the percent difference in FPF and MMAD between low and high flows by 1-2 orders of magnitude compared with current commercial devices. In conclusion, the new CC-3D inhalers produced extremely high-quality aerosols with little sensitivity to flow rate and are expected to deliver approximately 95% of the ED to the lungs. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Systemic activity of inhaled steroids in 1- to 3-year-old children with asthma

DEFF Research Database (Denmark)

Anhøj, Jacob; Bisgaard, Anne Marie; Bisgaard, Hans

2002-01-01

delivered via pressurized metered-dose inhaler (pMDI) and Babyhaler (FP400), was compared with budesonide, 200 microg twice daily delivered via pMDI and NebuChamber (BUD400), and to placebo. The Babyhaler was primed before use. Knemometry was used to detect systemic steroid activity. It was performed...... with a hand-held knemometer after 1 and 4 weeks of treatment. The increase in lower-leg length within this 3-week period was used as the outcome measure. The intention-to-treat population was analyzed by analysis of variance. RESULTS: The increases in the lower-leg length during placebo, BUD400, and FP400...... treatments were 85, 45, and 34 microm/d, respectively (adjusted mean). The growth in lower-leg length was significantly reduced from both steroid treatments. The difference between BUD400 and placebo was -40 microm/d (n = 25; 95% confidence interval [CI]: -8 to -72). The difference between FP400 and placebo...

Limitations of high dose carrier based formulations.

Science.gov (United States)

Yeung, Stewart; Traini, Daniela; Tweedie, Alan; Lewis, David; Church, Tanya; Young, Paul M

2018-06-10

This study was performed to investigate how increasing the active pharmaceutical ingredient (API) content within a formulation affects the dispersion of particles and the aerosol performance efficiency of a carrier based dry powder inhalable (DPI) formulation, using a custom dry powder inhaler (DPI) development rig. Five formulations with varying concentrations of API beclomethasone dipropionate (BDP) between 1% and 30% (w/w) were formulated as a multi-component carrier system containing coarse lactose and fine lactose with magnesium stearate. The morphology of the formulation and each component were investigated using scanning electron micrographs while the particle size was measured by laser diffraction. The aerosol performance, in terms of aerodynamic diameter, was assessed using the British pharmacopeia Apparatus E cascade impactor (Next generation impactor). Chemical analysis of the API was observed by high performance liquid chromatography (HPLC). Increasing the concentration of BDP in the blend resulted in increasing numbers and size of individual agglomerates and densely packed BDP multi-layers on the surface of the lactose carrier. BDP present within the multi-layer did not disperse as individual primary particles but as dense agglomerates, which led to a decrease in aerosol performance and increased percentage of BDP deposition within the Apparatus E induction port and pre-separator. As the BDP concentration in the blends increases, aerosol performance of the formulation decreases, in an inversely proportional manner. Concurrently, the percentage of API deposition in the induction port and pre-separator could also be linked to the amount of micronized particles (BDP and Micronized composite carrier) present in the formulation. The effect of such dose increase on the behaviour of aerosol dispersion was investigated to gain greater insight in the development and optimisation of higher dosed carrier-based formulations. Copyright © 2018 Elsevier B.V. All

Agglomerate behaviour of fluticasone propionate within dry powder inhaler formulations.

Science.gov (United States)

Le, V N P; Robins, E; Flament, M P

2012-04-01

Due to their small size, the respirable drug particles tend to form agglomerates which prevent flowing and aerosolisation. A carrier is used to be mixed with drug in one hand to facilitate the powder flow during manufacturing, in other hand to help the fluidisation upon patient inhalation. Depending on drug concentration, drug agglomerates can be formed in the mixture. The aim of this work was to study the agglomeration behaviour of fluticasone propionate (FP) within interactive mixtures for inhalation. The agglomerate phenomenon of fluticasone propionate after mixing with different fractions of lactose without fine particles of lactose (smaller than 32 μm) was demonstrated by the optical microscopy observation. A technique measuring the FP size in the mixture was developed, based on laser diffraction method. The FP agglomerate sizes were found to be in a linear correlation with the pore size of the carrier powder bed (R(2)=0.9382). The latter depends on the particle size distribution of carrier. This founding can explain the role of carrier size in de-agglomeration of drug particles in the mixture. Furthermore, it gives more structural information of interactive mixture for inhalation that can be used in the investigation of aerosolisation mechanism of powder. According to the manufacturing history, different batches of FP show different agglomeration intensities which can be detected by Spraytec, a new laser diffraction method for measuring aerodynamic size. After mixing with a carrier, Lactohale LH200, the most cohesive batch of FP, generates a lower fine particle fraction. It can be explained by the fact that agglomerates of fluticasone propionate with very large size was detected in the mixtures. By using silica-gel beads as ball-milling agent during the mixing process, the FP agglomerate size decreases accordingly to the quantity of mixing aid. The homogeneity and the aerodynamic performance of the mixtures are improved. The mixing aid based on ball

Effect of budesonide/formoterol pressurized metered-dose inhaler on exacerbations versus formoterol in chronic obstructive pulmonary disease: The 6-month, randomized RISE (Revealing the Impact of Symbicort in reducing Exacerbations in COPD) study.

Science.gov (United States)

Ferguson, Gary T; Tashkin, Donald P; Skärby, Tor; Jorup, Carin; Sandin, Kristina; Greenwood, Michael; Pemberton, Kristine; Trudo, Frank

2017-11-01

Prevention of exacerbations is a primary goal for chronic obstructive pulmonary disease (COPD) therapy. This randomized, double-blind, double-dummy, parallel-group, multicenter study evaluated the effect of budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus formoterol dry powder inhaler (DPI) on reducing COPD exacerbations. 1219 patients aged ≥40 years with moderate-to-very-severe COPD (per lung function) and a history of ≥1 COPD exacerbation received budesonide/formoterol pMDI 320/9 μg twice daily (BID) during a 4-week run-in. Patients were then randomized 1:1 to receive budesonide/formoterol pMDI 320/9 μg BID (n = 606) or formoterol DPI 9 μg BID (n = 613) for 26 weeks. Exacerbations were identified using predefined criteria for symptom worsening and treatment with systemic corticosteroids and/or antibiotics and/or hospitalization. The primary endpoint was annual rate of exacerbations. Budesonide/formoterol pMDI resulted in a 24% reduction in annual rate of exacerbations (0.85 vs 1.12; rate ratio: 0.76 [95% CI: 0.62, 0.92]; P = 0.006), and a significant risk reduction for time to first exacerbation (hazard ratio: 0.78 [95% CI: 0.64, 0.96]; P = 0.016) versus formoterol DPI. The most commonly reported adverse events (AEs; ≥3%) in budesonide/formoterol and formoterol groups were COPD (4.5% vs 8.6%) and nasopharyngitis (5.0% vs 5.2%). Pneumonia AEs were reported in 0.5% and 1.0% of budesonide/formoterol-treated and formoterol-treated patients, respectively. Budesonide/formoterol pMDI is an effective treatment option for reducing exacerbation rates in COPD patients with moderate-to-very-severe airflow limitation and history of exacerbations. No increase in pneumonia was observed with budesonide/formoterol; safety data were consistent with its established profile. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparative study of budesonide as a nebulized suspension vs pressurized metered-dose inhaler in adult asthmatics

DEFF Research Database (Denmark)

Bisgaard, H; Nikander, K; Munch, E

1998-01-01

The study objective was to compare the effect of budesonide administered as a nebulized suspension as compared to a spray with a spacer in adult asthmatics. In a double-blind, double-dummy crossover study, 26 adult patients with moderately severe unstable asthma were randomized to three 4-week...... treatment periods with budesonide 0.8 mg b.i.d. administered by a pressurized metered-dose inhaler (pMDI) with spacer (Nebuhaler) and budesonide 1 mg and 4 mg b.i.d. administered by a Pari Inhalier Boy jet nebulizer. The nebulizer was activated only during inspiration. The total mass output was similar from...... the two devices but their fraction of small particles differed by a factor of 2 in favour of pMDI. Effect was evaluated from daily home measurements of peak expiratory flow (PEF), need of beta 2-agonist and symptom scores. Plasma cortisol and budesonide levels were measured in a subgroup of 10 patients...

Which inhaled corticosteroid and long-acting β-agonist combination is better in patients with moderate-to-severe asthma, a dry powder inhaler or a pressurized metered-dose inhaler?

Science.gov (United States)

Muraki, Masato; Gose, Kyuya; Hanada, Soichiro; Sawaguchi, Hirochiyo; Tohda, Yuji

2017-11-01

Two main types of devices are used to facilitate the administration of inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) in combination, dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs). There are few reports comparing the effects of the two devices, and it is unknown which should be recommended for asthma patients with given sets of characteristics. In the current study, the beneficial effects and side effects associated with DPIs and pMDIs were compared, and the question of which device should be recommended for asthma patients was investigated. A prospective, randomized, crossover, comparative study in adult outpatients with asthma was conducted using salmeterol/fluticasone propionate combination (SFC) 50 μg/250 μg, one inhalation of Adoair ® 250 Diskus ® twice daily or two inhalations of Adoair ® 125 Aerosol twice daily, for 8 weeks. Questionnaires, exhaled nitric oxide (FeNO) tests and pulmonary function tests were administered after the use of each device for 8 weeks, and the results derived from each device were compared. Sixty-eight subjects were included in the final analysis. There were no significant differences between quality-of-life scores, FeNO, spirometry test results and forced oscillation results. With regard to patient preferences, 57.4% preferred the Adoair ® Aerosol and 35.3% preferred the Adoair ® Diskus ® , as determined via the comparative evaluation questionnaire. Although DPI prescription accounts for the predominant market share of combined ICS/LABA in Japan, patients preferred a pMDI device to a DPI device. Compared to DPIs, pMDIs may be the preferential choice for patients with asthma.

Brand and generic use of inhalation medication and frequency of switching in children and adults: A population-based cohort study.

Science.gov (United States)

Engelkes, Marjolein; van Blijderveen, Jan C; Overbeek, Jetty A; Kuiper, Josephine; Herings, Ron C M; Sturkenboom, Miriam C J M; de Jongste, Johan C; Verhamme, Katia M C; Janssens, Hettie M

2017-11-29

The expiration of patents of brand inhalation medications and the ongoing pressure on healthcare budgets resulted in a growing market for generics. To study the use of brand and generic inhalation medication and the frequency of switching between brand and generic and between devices. In addition, we investigated whether switching affected adherence. From dispensing data from the Dutch PHARMO Database Network a cohort aged ≥ 5 years, using ≥ 1 year of inhalation medication between 2003 and 2012 was selected. Switching was defined as changing from brand to generic or vice versa. In addition, we studied change in aerosol delivery device type (e.g., DPI, pMDI, and nebulizers). Adherence was calculated using the medication possession ratio (MPR). The total cohort comprised 70,053 patients with 1,604,488 dispensations. Per calendar year, 5% switched between brand and generic inhalation medication and 5% switched between devices. Median MPRs over the first 12 months ranged between 33 and 55%. Median MPR over the total period was lower after switch from brand to generic and vice versa for formoterol (44.5 vs. 42.1 and 63.5 vs. 53.8) and beclomethasone (93.8 vs. 59.8 and 81.3 vs. 55.9). Per year, switching between brand and generic inhalation medication was limited to 5% of the patients, switching between device types was observed in 5% as well. Adherence to both generic and brand inhalation medication was low. Effect of switching on adherence was contradictory; depending on time period, medication and type, and direction of switching. Further research on reasons for switching and potential impact on clinical outcomes is warranted.

Development and scintigraphic evaluation of submicron sized dry powder inhalation formulation of fluticasone propionate in healthy human volunteers

International Nuclear Information System (INIS)

Ali, Sultana S.; Ahmad, F.J.; Khar, R.K.; Rathore, V.P.; Ali, Rashid; Rawat, H.S.; Chopra, M.K.; Mittal, G.; Bhatnagar, A.

2010-01-01

Full text: Objective of the present study concerns formulation and evaluation of submicron sized dry powder inhalation formulation of Fluticasone propionate for the treatment of bronchial asthma, COPD and a new life saving treatment option in restrictive lung diseases such as Interstitial Lung Disease (ILD), toxic and non-cardiogenic pulmonary inflammations or pulmonary edema, which have no effective treatment presently. Materials and Methods: The submicron sized particles were prepared by precipitation method using acetone as solvent and water as antisolvent. Poloxamer F127 was used as stabilizer. Both submicronized and micronized particles were characterized using FTIR, XRD, DSC, SEM and TEM. The mass median aerodynamic diameter (MMAD) of the submicronized and micronized API was calculated using Andersen cascade impactor. The prepared particles and micronized Active Pharmaceutical Ingredient (API) were radiolabeled with 99m Tc. Size3 HPMC capsules were filled with the 12.5 mg radiolabeled blend (100μg Fluticasone propionate and 12.4mg inhalable lactose) and given to healthy volunteers to assess the comparative pulmonary deposition. Results: The prepared formulation has shown better lung deposition as compared to micronized API. The MMAD of submicronized particles was in the range of 1 - 5 μm while the MMAD of micronized API was in the range of 5 - 15μm. Conclusion: The developed submicron sized dry powder inhalation formulation has better lung deposition as compared to micron sized API and it will become a better treatment option for the bronchial asthma, COPD and ILDs

Inhalation of a dry powder ciprofloxacin formulation in healthy subjects: a phase I study.

Science.gov (United States)

Stass, Heino; Nagelschmitz, Johannes; Willmann, Stefan; Delesen, Heinz; Gupta, Abhishek; Baumann, Sybille

2013-06-01

Oral and intravenous formulations of ciprofloxacin have established efficacy and safety profiles in respiratory infections. A dry powder for inhalation (DPI) that uses Novartis' PulmoSphere™ technology has been developed to deliver high concentrations of ciprofloxacin to the lung with low systemic exposure using a portable and convenient passive dry powder inhaler (Novartis' T-326 inhaler). The primary objective was to investigate the safety and tolerability of ciprofloxacin DPI in healthy male subjects, with a secondary objective to investigate the pharmacokinetics of ciprofloxacin after ciprofloxacin DPI administration. This was a phase I, single-dose, single-site, randomized, single-blind, placebo-controlled, crossover study conducted in the hospital setting. Subjects were followed up for safety for approximately 2 weeks. Six healthy male subjects, aged 27-42 years with no history of pulmonary disease, repeated bronchitis or respiratory allergies were enrolled. In randomized order and separated by a 1-week washout period, subjects inhaled a single dose of ciprofloxacin DPI 32.5 mg or placebo from the T-326 inhaler. Primary safety parameters included vital signs, electrocardiogram, laboratory tests, adverse events and lung function (total specific resistance, thoracic gas volume and forced expiratory volume in 1 s). Plasma concentration-time data were used to calculate pharmacokinetic parameters. Ciprofloxacin DPI was well tolerated with no clinically relevant adverse effects on lung function. Estimates of lung deposition derived from physiology-based pharmacokinetic modelling suggest that approximately 40 % of the total dose of ciprofloxacin DPI reached the trachea/bronchi and alveolar space. Systemic ciprofloxacin was detected soon after inhalation [peak concentration in plasma (C(max)) 56.42 μg/L, median time to C max 0.625 h], but total systemic exposure was minimal (area under the plasma concentration-time curve 354.4 μg·h/L). Terminal elimination half

Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications.

Science.gov (United States)

Rudokas, Mindaugas; Najlah, Mohammad; Alhnan, Mohamed Albed; Elhissi, Abdelbary

2016-01-01

This is a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues relating to the mechanism of nebulisation and liposome composition were appraised and correlated with literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was liposome inhalation for the treatment of lung cancers. Many in vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated, including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localise their action in the lung following pulmonary delivery. The safety of inhaled liposomes incorporating anticancer drugs depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low doses reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases, including pulmonary cancers. The successful development of anticancer liposomes for inhalation may depend on the future development of effective aerosolisation devices and better targeted liposomes to maximise the benefit of therapy and reduce the potential for local and systemic adverse effects. © 2016 S. Karger AG, Basel.

Identification of inhaler technique errors with a routine procedure in Portuguese community pharmacy

Directory of Open Access Journals (Sweden)

Castel-Branco MM

2017-12-01

Full Text Available Background: A correct selection of drugs prescribed, but also the choice of the appropriate inhaler device, is crucial for the control of respiratory diseases. Objective: To evaluate the inhaler technique and identify potential errors of patients when treated with inhalers by testing a routinary procedure to be implemented in any community pharmacy. Methods: Adults with asthma/COPD and under inhalation therapy were invited to demonstrate how they use their inhalers. After direct observation it was registered whether all the sequential steps included in the summary of product characteristics (SmPC were performed. Results: The study involved 67 patients from 4 community pharmacies (Portugal central region: 34 (50.7% males, 65.4 (SD=18.28 years old, 42 (62.7% with COPD, and 23 (34.3% using more than one inhaler. The 67 patients used 95 inhalers, comprising: 57 (60.0% multiple dose DPI (dry powder inhalers, 18 (18.9% single dose DPI, 16 (16.8% pMDI (pressurized metered dose inhalers, 2 (2.1% pMDI+spacer and 2 (2.1% SMI (soft mist inhalers. No errors were made only by 9 (13.4% patients. In the 75 DPIs techniques, the most frequent errors were ‘no previous forced expiration’ (46=61.3% and ‘no 10s apnea after inhalation’ (51=68.0%; in the 16 pMDIs techniques common errors were ‘lack of hand-lung coordination’ (7=43.8 %, ‘no previous forced exhalation’ (8=50.0% and ‘no apnea after inhalation’ (10=62.5%. After inhaling from 56 devices containing corticosteroids, 34 (60.7% of the patients did not wash their mouth. Conclusion: The study demonstrated the possibility of performing this procedure routinely in Portuguese community pharmacies and also its utility, since 58 (87% of patients had at least one error during the inhalers use.

Development of an Improved Inhalable Powder Formulation of Pirfenidone by Spray-Drying: In Vitro Characterization and Pharmacokinetic Profiling.

Science.gov (United States)

Seto, Yoshiki; Suzuki, Gen; Leung, Sharon Shui Yee; Chan, Hak-Kim; Onoue, Satomi

2016-06-01

Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method. Spray-dried PFD (SD/PFD) was prepared by spray-drying with L-leucine, and the physicochemical properties and efficacy in an antigen-sensitized airway inflammation model were assessed. A pharmacokinetic study was also conducted after intratracheal and oral administration of PFD formulations. Regarding powder characterization, SD/PFD had dimpled surface with the mean diameter of 1.793 μm. In next generation impactor analysis, SD/PFD demonstrated high in vitro inhalation performance without the need of carrier particles, and the fine particle fraction of SD/PFD was calculated to be 62.4%. Insufflated SD/PFD (0.3 mg-PFD/rat) attenuated antigen-evoked inflammatory events in the lung, including infiltration of inflammatory cells and myeloperoxidase activity. Systemic exposure level of PFD after insufflation of SD/PFD at the pharmacologically effective dose was 600-fold lower than that after oral administration of PFD at the phototoxic dose. SD/PFD would be suitable for inhalation, and the utilization of an RP system with SD/PFD would provide a safer medication compared with oral administration of PFD.

Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence

Science.gov (United States)

Lacalle Muls, Helena; Costello, Richard W.; Reilly, Richard B.

2018-01-01

Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be

Impact of extrafine formulations of inhaled corticosteroids/long-acting beta-2 agonist combinations on patient-related outcomes in asthma and COPD

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Scichilone N

2014-11-01

Full Text Available Nicola Scichilone,1 Alida Benfante,1 Luca Morandi,2 Federico Bellini,2 Alberto Papi21Biomedical Department of Internal and Specialist Medicine, Section of Pulmonology, University of Palermo, Italy; 2Respiratory Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, ItalyAbstract: Asthma and chronic obstructive pulmonary disease (COPD are among the most common chronic diseases worldwide, characterized by a condition of variable degree of airway obstruction and chronic airway inflammation. A large body of evidence has demonstrated the importance of small airways as a pharmacological target in these clinical conditions. Despite a deeper understanding of the pathophysiological mechanisms, the epidemiological observations show that a significant proportion of asthmatic and COPD patients have a suboptimal (or lack of control of their diseases. Different factors could influence the effectiveness of inhaled treatment in chronic respiratory diseases: patient-related (eg, aging; disease-related (eg, comorbid conditions; and drug-related/formulation-related factors. The presence of multiple illnesses is common in the elderly patient as a result of two processes: the association between age and incidence of degenerative diseases; and the development over time of complications of the existing diseases. In addition, specific comorbidities may contribute to impair the ability to use inhalers, such as devices for efficient drug delivery in the respiratory system. The inability to reach and treat the peripheral airways may contribute to the lack of efficacy of inhaled treatments. The recent development of inhaled extrafine formulations allows a more uniform distribution of the inhaled treatment throughout the respiratory tree to include the peripheral airways. The beclomethasone/formoterol extrafine formulation is available for the treatment of asthma and COPD. Different biomarkers of peripheral airways are improved by beclomethasone

An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma

Science.gov (United States)

Reolon, Luciano Antonio; Amaral-Machado, Lucas; Gremião, Maria Palmira Daflon; Guterres, Silvia S.

2018-01-01

Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU) for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a) 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS) and (b) 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS). The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS) and 1.138 ± 0.54 µm (5FU-MS). The fraction of respirable particles (FR%) were 76.84 ± 0.07% (5FU-NS) and 55.01 ± 2.91% (5FU-MS). The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375) and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively. PMID:29385692

An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma

Directory of Open Access Journals (Sweden)

Kelly Cristine Zatta

2018-01-01

Full Text Available Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS and (b 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS. The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS and 1.138 ± 0.54 µm (5FU-MS. The fraction of respirable particles (FR% were 76.84 ± 0.07% (5FU-NS and 55.01 ± 2.91% (5FU-MS. The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375 and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively.

Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized Bed Design.

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Farkas, Dale R; Hindle, Michael; Longest, P Worth

2015-11-01

The objective of this study was to develop a new high-efficiency dry powder inhaler (DPI) that can effectively aerosolize large masses (25-100 mg) of spray dried powder formulations. The DPI was designed to implement a concept similar to a fluidized bed for aerosolization using small mixing balls made of polytetrafluoroethylene along with a larger, hollow dosing sphere filled with the powder. The performance of the fluidized bed DPI was compared, based on emitted dose (ED) and aerosolization efficiency, to other recently developed capsule-based DPIs that were designed to accommodate smaller powder masses (~2-20 mg). The inhalers were tested with spray dried excipient enhanced growth (EEG) formulations that contained an antibiotic (ciprofloxacin) and hygroscopic excipient (mannitol). The new fluidized bed design produced an ED of 71% along with a mass median aerodynamic diameter of 1.53 μm and fine particle fractions <5 and 1 μm of 93 and 36%, respectively, when used to deliver a 100 mg loaded mass of EEG powder with the advantage of not requiring multiple capsules. Surprisingly, performance of the device was further improved by removing the mixing balls from the inhaler and only retaining the dose containment sphere.

Can patients with asthma feel inhaler therapy working right away? Two clinical trials testing the effect of timing of assessment on patient perception.

Science.gov (United States)

Leidy, Nancy Kline; Gutierrez, Benjamin; Lampl, Kathy; Uryniak, Tom; O'Brien, Christopher D

2009-12-01

Feeling a maintenance therapy work right away may provide positive reinforcement and may offer one way to improve adherence in patients with asthma. Precise measurement is required to accurately compare the presence of this effect across clinical trial treatment groups. Two randomized, controlled studies tested whether timing of assessment (daily vs weekly, study 1; and predose vs postdose, study 2) influenced patients' reports of whether they can feel a medication working right away (perception), and their satisfaction with this perception (satisfaction). These 2-week US-based multicenter double-blind, parallel-group studies included patients > or = 18 years of age with mild to moderate persistent asthma. In each, patients were randomized to one of two drugs with different onset profiles: budesonide/formoterol pressurized metered-dose inhaler (pMDI) 80/4.5 microg x 2 inhalations (160/9 microg) twice daily or budesonide pMDI 80 microg x 2 inhalations (160 microg) twice daily. Patients were further randomized to complete previously validated perception and satisfaction questions in a cross-over fashion, either daily and weekly (N = 123) or predose and postdose (N = 134). Patient surveys also assessed perceptions of the onset of effect of medication and their value of these perceptions. No significant differences were observed in patients' reports of perception, either daily versus weekly or predose versus postdose. A statistically significant difference in satisfaction was found in study 1 only, favoring weekly recall (p away (136 of 157 patients) identified positive airway sensations. Most patients reported that feeling their medication work right away is reassuring and would help them manage their asthma. Assessment timing has no effect on patient response to the perception of feeling a medication working right away. Differences found in satisfaction levels reported with weekly versus daily recall were consistent across treatment groups, indicating that no bias

Development and assessment of countermeasure formulations for treatment of lung injury induced by chlorine inhalation

Energy Technology Data Exchange (ETDEWEB)

Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Chen, Jing; Schlueter, Connie F.; Mo, Yiqun; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Rawson, Greg; Niño, Joe A.; Carson, Kenneth H. [Microencapsulation and Nanomaterials Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX (United States)

2016-05-01

Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Countermeasures for treatment of chlorine-induced acute lung injury are needed. • Formulations containing rolipram, triptolide, or budesonide were produced. • Formulations with a wide range of release properties were developed. • Countermeasure formulations inhibited chlorine-induced lung injury in mice.

Forecasting of development of acute poisonings in agricultural workers while using combined formulations based on difenoconazole

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Stavnichenko P.V.

2017-10-01

Full Text Available In the general structure of occupational diseases, a large proportion belongs to acute poisoning with pesticides (mainly group cases. However, today it is impossible to drop the use of pesticides in agriculture. Their application ensures high biological and economic efficiency of the latter, reduces losses of the yield. The purpose of the work was to predict the possibility of acute toxic effects in agricultural workers when working with combined formulations based on difenoconazole. Materials and methods. To assess the influence on the organism of the workers of the above-mentioned substances and formulations on their basis, the coefficient of inhalation poisoning possibility (CIPP, the coefficient of selective action of the pesticide in inhalation effect (CSAing and the selective action of the pesticide in the dermal effect (CSAderm were calculated. Results. Calculated values of CSAing (103.4-4701.2 and CSAderm (237.4-12345.7 for all investigated active substances were more than 100, this indicates to a rather high selectivity of their action. By the CSAing value formulations Celeste Top, Celeste Trio, Dinali, Cydeli Top belong to pesticides with a relatively low selectivity of action when they are inhaled by workers in the process of crops treating, the remaining formulations have a sufficient selectivity of action in inhalation intake. In addition, it should be noted that in general, for all combined preparations CSA values are significantly lower than for separate active ingredients, in addition to the above assumption, can be explained by the presence of other formulants in the preparation that may have not significant but toxic effect on the body of workers. All investigated substances in the probability of occurrence of acute poisoning with the use of combined preparations on their basis are related to the 4th grade of danger according to State Standards 8.8.1.002-98. There was proved relative safety in case of penetration into the

The influence of high shear mixing on ternary dry powder inhaler formulations.

Science.gov (United States)

Hertel, Mats; Schwarz, Eugen; Kobler, Mirjam; Hauptstein, Sabine; Steckel, Hartwig; Scherließ, Regina

2017-12-20

The blending process is a key step in the production of dry powder inhaler formulations, but only little is known about the influence of process parameters. This is especially true for high shear blending of ternary formulations. For this reason, this study aims to investigate the influence of high shear mixing process parameters (mixing time and rotation speed) on the fine particle fraction (FPF) of ternary mixtures when using budesonide as model drug, two different carrier materials and two different mixing orders. Prolonged mixing time and higher rotation speeds led to lower FPFs, possibly due to higher press-on forces acting on the active pharmaceutical ingredients (API). In addition, a clear correlation between the energy consumption of the blender (the energy input into the blend) and the reduction of the FPF could be shown. Furthermore blending the carrier and the fines before adding the API was also found to be favorable. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhalation of amphotericin B formulations for prevention and treatment of invasive pulmonary aspergillosis : an experimental study in rats

NARCIS (Netherlands)

E.J. Ruijgrok (Elisabeth)

2002-01-01

textabstractBecause current knowledge of inhalational AMB is limited, a rigorous scientific approach is warranted to establish opt"1mal dose, frequency and durat"1on of administration. We therefore decided to study in detail the fu II potential of nebulised AMB in different formulations, with the

Aerosol formulation and clinical efficacy of bronchodilators

NARCIS (Netherlands)

Zanen, Pieter

1998-01-01

This thesis subject is the improvement of the formulation of inhaled aerosols. It is well known that the formulation of inhaled drugs is not optimal: the major part of the mass delivered does not reach the lower airways. This phenomenon is due to the particle size of the inhaled particles, which

Conference report: 1st Medicon Valley Inhalation Symposium.

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Lastow, Orest

2013-02-01

The 1st Medicon Valley Inhalation Symposium was arranged by the Medicon Valley Inhalation Consortium. It was held at the Medicon Village site, which is the former AstraZeneca site in Lund, Sweden. It was a 1-day symposium focused on inhaled drug delivery and inhalation product development. A total of 90 delegates listened to 15 speakers. The program was organized to follow the value chain of an inhalation product development. The benefits and future opportunities of inhaled drug delivery were discussed together with some new disease areas that can be targeted with inhalation. The pros and cons of the two main formulation types; dry powder and liquid formulations, were discussed by a panel. The different requirements of the drug molecules from a pharmacology, chemical and physical perspective were explained. The modeling of the physics inside an inhaler was demonstrated and the potential strategic benefits of device design were highlighted together with the many challenges of formulation manufacturing. Lung deposition mechanisms and the difficulties of the generic bioequivalence concept were discussed. Using an anatomically correct impactor inlet is a valuable tool in lung deposition predictions and the planning of clinical trials. The management of the biological material generated in clinical studies is key to successful studies.

Development of a High Efficiency Dry Powder Inhaler: Effects of Capsule Chamber Design and Inhaler Surface Modifications

Science.gov (United States)

Behara, Srinivas R.B.; Farkas, Dale R.; Hindle, Michael; Longest, P. Worth

2013-01-01

Purpose The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. Methods DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. Results The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. Conclusions High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD 90%, and ED > 80%. PMID:23949304

Development of a high efficiency dry powder inhaler: effects of capsule chamber design and inhaler surface modifications.

Science.gov (United States)

Behara, Srinivas R B; Farkas, Dale R; Hindle, Michael; Longest, P Worth

2014-02-01

The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD  90%, and ED > 80%.

Investigating the reactivity of pMDI with wood cell walls using high-resolution solution-state NMR spectroscopy

Science.gov (United States)

Daniel J. Yelle; John Ralph; Charles R. Frihart

2009-01-01

The objectives of this study are the following: (1) Use solution-state NMR to assign contours in HSQC spectra of the reaction products between pMDI model compounds and: (a) lignin model compounds, (b) milled-wood lignin, (c) ball-milled wood, (d) microtomed loblolly pine; (2) Determine where and to what degree urethane formation occurs with loblolly pine cell wall...

Inhaled antibiotics for lower airway infections.

Science.gov (United States)

Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W

2014-03-01

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

Inhaled corticosteroid metered-dose inhalers: how do variations in technique for solutions versus suspensions affect drug distribution?

Science.gov (United States)

Robinson, Christie A; Tsourounis, Candy

2013-03-01

To assess the literature that evaluates how variations in metered-dose inhaler (MDI) technique affect lung distribution for inhaled corticosteroids (ICSs) formulated as MDI suspensions and solutions. PubMed (up to November 2012) and Cochrane Library (up to November 2012) were searched using the terms metered-dose inhalers, HFA 134a, Asthma/*drug therapy, and inhaled corticosteroids. In addition, reference citations from publications identified were reviewed. All articles in English from the data sources that assessed MDI technique comparing total lung distribution (TLD) of MDI solutions or suspensions formulated with ICSs were included in the review. Five relevant studies were identified. Five controlled studies compared how variations in MDI technique affect TLD for ICS MDI solutions with suspensions. MDI solutions resulted in greater TLD compared with larger particle MDI suspensions. Delayed or early inspiration upon device actuation of MDI solutions resulted in less TLD than coordinated actuation, but with a 3- to 4-times greater TLD than MDI suspensions inhaled using a standard technique. A sixth study evaluated inspiratory flow rates (IFR) for small, medium, and large particles. Rapid and slow IFRs resulted in similar TLD for small particles, while far fewer particles reached the airways with medium and large particles at rapid, rather than slow, IFRs. Based on the literature evaluated, standard MDI technique should be used for ICS suspensions. ICS MDI solutions can provide a higher average TLD than larger-particle ICS suspensions using standard technique, discoordinated inspiration and medication actuation timing, or rapid and slow IFRs. ICS MDI solutions allow for a more forgiving technique, which makes them uniquely suitable options for patients with asthma who have difficultly with MDI technique.

Inhalation drug delivery devices: technology update

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Ibrahim M

2015-02-01

Full Text Available Mariam Ibrahim, Rahul Verma, Lucila Garcia-ContrerasDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided.Keywords: pulmonary delivery, asthma, nebulizers, metered dose inhaler, dry powder inhaler

Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

DEFF Research Database (Denmark)

Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle

2013-01-01

The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

Physicochemical characteristics of chlorofluorohydrocarbon-based inhalation aerosols

Energy Technology Data Exchange (ETDEWEB)

Ashurst, I C

1985-01-01

The aim of this work was to gain a better understanding of the physicochemical factors which affect the formulation of suspension inhalation aerosols. The adsorption of six nonionic and cationic surfactants onto Spherisorb has been investigated. The results were analyzed by calculating the area occupied by one adsorbed molecule at the surface and by comparing these values for each surfactant. The amount of each surfactant adsorbed was correlated with the number of sites on that surfactant molecule which could interact with the surface. The stability of suspensions, produced by both the model colloid Spherisorb, and by the drug isoprenaline sulfate, after adsorption of the surfactants, has been assessed by measuring settling times and rising times. The most stable suspension were found to be those which had the greatest amounts of long chain fatty acid surfactant adsorbed on their surface. A comparison was made between the effective stabilizing properties of Span 85 and oleic acid on various drug suspension. It was found that Span 85 gave the most stable suspension. Inhalation aerosol suspensions of isoprenaline sulfate were manufactured using the same surfactants used in the adsorption and suspension stability studies and were analyzed by measuring the particle size distributions of the suspension and the emitted doses. The results were found to correlate with the adsorption and suspension stability studies and it was concluded that a deflocculated suspension was preferable to a flocculated suspension in inhalation aerosols provided that the drug density was less than the propellant density. The application of this work to preformulation studies was also discussed.

Imagine the Superiority of Dry Powder Inhalers from Carrier Engineering

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Piyush Mehta

2018-01-01

Full Text Available Inhalation therapy has strong history of more than 4000 years and it is well recognized around the globe within every culture. In early days, inhalation therapy was designed for treatment of local disorders such as asthma and other pulmonary diseases. Almost all inhalation products composed a simple formulation of a carrier, usually α-lactose monohydrate orderly mixed with micronized therapeutic agent. Most of these formulations lacked satisfactory pulmonary deposition and dispersion. Thus, various alternative carrier’s molecules and powder processing techniques are increasingly investigated to achieve suitable aerodynamic performance. In view of this fact, more suitable and economic alternative carrier’s molecules with advanced formulation strategies are discussed in the present review. Furthermore, major advances, challenges, and the future perspective are discussed.

Inhaled antibiotics for lower respiratory tract infections: focus on ciprofloxacin.

Science.gov (United States)

Serisier, D J

2012-05-01

The administration of antibiotics by the inhaled route offers an appealing and logical approach to treating infectious respiratory conditions. Studies in the cystic fibrosis (CF) population have established the efficacy of this therapeutic concept and inhaled antibiotic therapy is now one of the pillars of management in CF. There are now a number of new inhaled antibiotic formulations that have shown impressive preliminary evidence for efficacy in CF and are commencing phase III efficacy studies. Translation of this paradigm into the non-CF bronchiectasis population has proven difficult thus far, apparently due to problems with tolerability of inhaled formulations. Inhaled versions of ciprofloxacin have shown good tolerability and microbiological efficacy in preliminary studies, suggesting that effective inhaled antibiotics are finally on the horizon for this previously neglected patient population. The increased use of long-term inhaled antibiotics for a wider range of non-CF indications presents risks to the broader community of greater antimicrobial resistance development that must be carefully weighed against any demonstrated benefits. Copyright 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Repurposing rosiglitazone, a PPAR-γ agonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH.

Science.gov (United States)

Rashid, Jahidur; Alobaida, Ahmad; Al-Hilal, Taslim A; Hammouda, Samia; McMurtry, Ivan F; Nozik-Grayck, Eva; Stenmark, Kurt R; Ahsan, Fakhrul

2018-06-28

Peroxisome-proliferator-activated-receptor-gamma (PPAR-γ) is implicated, in some capacity, in the pathogenesis of pulmonary arterial hypertension (PAH). Rosiglitazone, an oral antidiabetic and PPAR-γ agonist, has the potential to dilate pulmonary arteries and to attenuate arterial remodeling in PAH. Here, we sought to test the hypothesis that rosiglitazone can be repurposed as inhaled formulation for the treatment of PAH. We have tested this conjecture by preparing and optimizing poly(lactic-co-glycolic) acid (PLGA) based particles of rosiglitazone, assessing the drug particles for pulmonary absorption, investigating the efficacy of the plain versus particulate drug formulation in improving the respiratory hemodynamics in PAH animals, and finally studying the effect of the drug in regulating the molecular markers associated with PAH pathogenesis. The optimized particles were slightly porous and spherical, and released 87.9% ± 6.7% of the drug in 24 h. The elimination half-life of the drug formulated in PLGA particles was 2.5-fold greater than that of the plain drug administered via the same route at the same dose. The optimized formulation, given via the pulmonary route, produced pulmonary selective vasodilation in PAH animals, but oral rosiglitazone had no effect in pulmonary hemodynamics. Rosiglitazone ameliorates the pathogenesis of PAH by balancing the molecular regulators involved in the vasoconstriction and vasodilation of human pulmonary arterial smooth muscle cells. All in all, data generated using intact animal and cellular models point to the conclusion that PLGA particles of an antidiabetic drug can be used for the treatment of a different disease, PAH. Copyright © 2018 Elsevier B.V. All rights reserved.

Modeling Heat Transfer and Pressurization of Polymeric Methylene Diisocyanate (PMDI) Polyurethane Foam in a Sealed Container.

Energy Technology Data Exchange (ETDEWEB)

Scott, Sarah Nicole

2018-01-01

Polymer foam encapsulants provide mechanical, electrical, and thermal isolation in engineered systems. It can be advantageous to surround objects of interest, such as electronics, with foams in a hermetically sealed container to protect the electronics from hostile en vironments, such as a crash that produces a fire. However, i n fire environments, gas pressure from thermal decomposition of foams can cause mechanical failure of the sealed system . In this work, a detailed study of thermally decomposing polymeric methylene diisocyanate (PMDI) - polyether - polyol based polyurethane foam in a sealed container is presented . Both experimental and computational work is discussed. Three models of increasing physics fidelity are presented: No Flow, Porous Media, and Porous Media with VLE. Each model us described in detail, compared to experiment , and uncertainty quantification is performed. While the Porous Media with VLE model matches has the best agreement with experiment, it also requires the most computational resources.

Identification of factors involved in medication compliance: incorrect inhaler technique of asthma treatment leads to poor compliance

Directory of Open Access Journals (Sweden)

Darbà J

2016-02-01

Full Text Available Josep Darbà,1 Gabriela Ramírez,2 Antoni Sicras,3 Laura García-Bujalance,4 Saku Torvinen,5 Rainel Sánchez-de la Rosa6 1Department of Economics, Universitat de Barcelona, 2BCN Health Economics & Outcomes Research S.L., 3Department of Planning, Badalona Serveis Assistencials S.A., Barcelona, 4Market Access Department, Teva Pharmaceutical, Madrid, Spain; 5Market Access Department, Teva Pharmaceuticals Europe BV, Amsterdam, the Netherlands; 6Medical Department, Teva Pharmaceutical, Madrid, Spain Objective: To identify the impact of delivery device of inhaled corticosteroids and long-acting β2-agonist (ICS/LABA on asthma medication compliance, and investigate other factors associated with compliance. Materials and methods: We conducted a retrospective and multicenter study based on a review of medical registries of asthmatic patients treated with ICS/LABA combinations (n=2,213 whose medical devices were either dry powder inhalers (DPIs, such as Accuhaler®, Turbuhaler®, and NEXThaler® or pressurized metered-dose inhalers (pMDI. Medication compliance included persistence outcomes through 18 months and medication possession ratios. Data on potential confounders of treatment compliance such as asthma exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also explored. Results: The probability of asthma medication compliance in case of DPIs was lower compared to pMDIs, which suggests that inhaler devices influence inhalation therapies. There were additional confounding factors that were considered as explanatory variables of compliance. A worse measure of airflow obstruction (forced expiration volume in 1 second, comorbidities and general practitioner (GP consultations more than once per month decreased the probability of compliance. Within comorbidities, alcoholism was positively associated with compliance. Patients of 29–39, 40–50, and 51–61 age groups or suffering from more than two

Reverse water-in-fluorocarbon emulsions for use in pressurized metered-dose inhalers containing hydrofluoroalkane propellants.

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Butz, N; Porté, C; Courrier, H; Krafft, M P; Vandamme, Th F

2002-05-15

Pulmonary administration of drugs has demonstrated numerous advantages in the treatment of pulmonary diseases due to direct targeting to the respiratory tract. It enables avoiding the first pass effect, reduces the amount of drugs administered, targets drugs to specific sites and reduces their side effects. Reverse water-in-fluorocarbon (FC) emulsions are potential drug delivery systems for pulmonary administration using pressurized metered-dose inhalers (pMDI). The external phase of these emulsions consists of perfluorooctyl bromide (PFOB, perflubron), whereas their internal phase contains the drugs solubilized or dispersed in water. These emulsions are stabilized by a perfluoroalkylated dimorpholinophosphate (F8H11DMP), i.e. a fluorinated surfactant. This study demonstrates the possibility of delivering a reverse fluorocarbon emulsion via the pulmonary route using a CFC-free pMDI. Two hydrofluoroalkanes (HFAs) (Solkane(R) 134a and Solkane(R) 227) were used as propellants, and various solution (or emulsion)/propellant ratios (1/3, 1/2, 2/3, 1/1, 3/2, 3/1 v/v) were investigated. The insolubility of water (with or without the fluorinated surfactant F8H11DMP) in both HFA 227 and HFA 134a was demonstrated. PFOB and the reverse emulsion were totally soluble or dispersible in all proportions in both propellants. This study demonstrated also that the reverse FC emulsion can be successfully used to deliver caffeine in a homogeneous and reproducible way. The mean diameter of the emulsion water droplets in the pressured canister was investigated immediately after packaging and after 1 week of storage at room temperature. Best results were obtained with emulsion/propellant ratios comprised between 2/3 and 3/2, and with HFA 227 as propellant.

Delineating pMDI model reactions with loblolly pine via solution-state NMR spectroscopy. Part 1, Catalyzed reactions with wood models and wood polymers

Science.gov (United States)

Daniel J. Yelle; John Ralph; Charles R. Frihart

2011-01-01

To better understand adhesive interactions with wood, reactions between model compounds of wood and a model compound of polymeric methylene diphenyl diisocyanate (pMDI) were characterized by solution-state NMR spectroscopy. For comparison, finely ground loblolly pine sapwood, milled-wood lignin and holocellulose from the same wood were isolated and derivatized with...

Cellular internalization and transport of biodegradable polyester dendrimers on a model of the pulmonary epithelium and their formulation in pressurized metered-dose inhalers.

Science.gov (United States)

Heyder, Rodrigo S; Zhong, Qian; Bazito, Reinaldo C; da Rocha, Sandro R P

2017-03-30

The purpose of this study was to evaluate the effect of generation and surface PEGylation of degradable polyester-based dendrimers nanocarriers on their interactions with an in vitro model of the pulmonary epithelium as well as to assess the ability to formulate such carriers in propellant-based, portable oral-inhalation devices to determine their potential for local and systemic delivery of drugs to and through the lungs. Hydroxyl (-OH) terminated polyester dendrimers of generation 3 and 4 (G3, and G4) were synthesized using a divergent approach. G4 was surface-modified with PEG (1,000Da). All dendrimers and their building blocks were determined to be highly compatible with the model pulmonary epithelium, with toxicity profiles much more favorable than non-degradable polyamidoamine dendrimers (PAMAM). The transport of the species from the apical to basolateral side across polarized Calu-3 monolayers showed to be generation and surface-chemistry (PEGylation) dependent. The extent of the transport is modulated by their interaction with the polarized epithelium and their transient opening of the tight junctions. G3 was the one most efficiently internalized by the epithelium, and had a small impact on the integrity of the monolayer. On the other hand, the PEGylated G4 was the one least internalized by the polarized epithelium, and at the same time had a more pronounced transient impact on the cellular junctions, resulting in more efficient transport across the cell monolayer. PEGylation of the dendrimer surface played other roles as well. PEGylation modulated the degradation profile of the dendrimer, slowing the process in a step-wise fashion - first the PEG layer is shed and then the dendrimer starts degrading. PEGylation also helped increase the solvation of the nanocarriers by the hydrofluoroalkane propellant used in pressurized metered-dose inhalers, resulting in formulations with excellent dispersibility and aerosol quality (deep lung deposition of 88

Inhaled antibiotics in the treatment of non-cystic fibrosis bronchiectasis: clinical and drug delivery perspectives.

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Sugianto, Tiffanie Daisy; Chan, Hak-Kim

2016-01-01

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive, suppurative lung disease characterized by permanent dilatation of bronchial subdivisions, which further causes accumulation of sputum and bacterial infections. The advent of inhaled antibiotics over the past two decades has been expected to effectively attenuate the problem of chronic bacterial infections in CF and NCFB subjects with higher, local drug concentrations and minimal systemic side effects. This review summarizes and evaluates current clinical evidence of efficacy and adverse effects of inhaled antibiotics in NCFB, as well as ongoing preclinical and clinical studies, followed by a discussion of issues and challenges in clinical practice and drug delivery strategies, together with future research directions. The evidence base of the clinical efficacy of inhaled antibiotics in NCFB is limited and the degrees of reported clinical benefits have been modest and conflicting. Challenges surrounding inhaled antibiotics application and development include the lack of knowledge of disease factors and optimum management strategies, unreceptive lung pathophysiology and the lack of factors that support compliance and tolerability. Nonetheless, research continues to give birth to new clinical findings and novel formulations such as combination antibiotics and sustained-release formulations, which add great value to the development of efficacious, safe and convenient inhalable antibiotics of the future.

Formulation and evaluation and terbutaline sulphate and ...

African Journals Online (AJOL)

We report the use of low rugosity lactose, product of controlled crystallization of this carrier, in the formulation of terbutaline sulphate and beclomethasone dipropionate dry powder inhalers. The deposition patterns obtained with inhalation mixtures consisting of the modified lactose and each of the micronised drugs ...

Impact of selected construction elements of capsule-based dry powder inhalers on the manner of drug delivery to the lungs

Directory of Open Access Journals (Sweden)

Marcin Odziomek

2016-12-01

Full Text Available The article discusses selected issues related to construction and performance of dry powder inhalers with the spinning capsule: Aerolizer® and cyclohaler. Investigations involved devices and capsules found among medicinal products available on the domestic market. Based on scanning electron microscope images, the following were determined: (i shape and crosssection of needles used to puncture drug-containing capsules as well as (ii size, geometry and cross-section of small holes in the capsules through which powder is introduced into the airstream while using the inhaler. It was found that differences in shape and spatial arrangement of needles affect both the total area of holes and the character of perforation. In Aerolizer® inhalers, the average area of holes is 1.3 mm2 at each side of the capsule, and oval through holes are obtained. In investigated cyclohaler-type inhalers, the average hole area ranges from 1.6 to 2.2 mm2, and perforations are partly covered by torn fragments of the capsule. It has been determined that both the type of needles and inherent properties of the material from which capsules are made have an impact on observed effects. The authors have also assessed the potential influence of differences in the manner of perforation and applied capsule material on even powder release and aerosol generation in the device. Also, attention has been paid to other significant features of inhaler devices and powder formulations which decide about effective inhalation drug delivery to the respiratory system.

Effect of processing history on the surface interfacial properties of budesonide in carrier-based dry-powder inhalers.

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Shur, Jagdeep; Pitchayajittipong, Chonladda; Rogueda, Philippe; Price, Robert

2013-08-01

Influence of air-jet micronization, post-micronization conditioning and storage on the surface properties of budesonide in dry-powder inhaler formulations was investigated. Crystalline budesonide was air jet-micronized and conditioned using organic vapor. Particle engineering was also used to fabricate respirable particles of budesonide. Surface imaging by atomic force microscopy suggested that micronized material possessed process-induced surface disorder, which relaxed upon conditioning with organic vapor. Particle engineered material was devoid of such surface disorder. Surface interfacial properties of all batches were different and correlated to in vitro fine particle delivery. The surface properties and in vitro performance of the conditioned material changed upon storage of the budesonide at 44% relative humidity and 25°C, while the micronized and particle-engineered material remained stable. These data suggest that processing conditions of budesonide affected the surface properties of the material, which was demonstrated to have direct affect on dry-powder inhaler formulation performance.

Experiments to populate and validate a processing model for polyurethane foam. BKC 44306 PMDI-10

Energy Technology Data Exchange (ETDEWEB)

Mondy, Lisa Ann [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rao, Rekha Ranjana [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Shelden, Bion [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Soehnel, Melissa Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); O' Hern, Timothy J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Grillet, Anne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Celina, Mathias C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wyatt, Nicholas B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Russick, Edward Mark [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bauer, Stephen J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hileman, Michael Bryan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Urquhart, Alexander [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Thompson, Kyle Richard [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Smith, David Michael [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2014-03-01

We are developing computational models to elucidate the expansion and dynamic filling process of a polyurethane foam, PMDI. The polyurethane of interest is chemically blown, where carbon dioxide is produced via the reaction of water, the blowing agent, and isocyanate. The isocyanate also reacts with polyol in a competing reaction, which produces the polymer. Here we detail the experiments needed to populate a processing model and provide parameters for the model based on these experiments. The model entails solving the conservation equations, including the equations of motion, an energy balance, and two rate equations for the polymerization and foaming reactions, following a simplified mathematical formalism that decouples these two reactions. Parameters for the polymerization kinetics model are reported based on infrared spectrophotometry. Parameters describing the gas generating reaction are reported based on measurements of volume, temperature and pressure evolution with time. A foam rheology model is proposed and parameters determined through steady-shear and oscillatory tests. Heat of reaction and heat capacity are determined through differential scanning calorimetry. Thermal conductivity of the foam as a function of density is measured using a transient method based on the theory of the transient plane source technique. Finally, density variations of the resulting solid foam in several simple geometries are directly measured by sectioning and sampling mass, as well as through x-ray computed tomography. These density measurements will be useful for model validation once the complete model is implemented in an engineering code.

Comparison of small-group training with self-directed internet-based training in inhaler techniques.

Science.gov (United States)

Toumas, Mariam; Basheti, Iman A; Bosnic-Anticevich, Sinthia Z

2009-08-28

To compare the effectiveness of small-group training in correct inhaler technique with self-directed Internet-based training. Pharmacy students were randomly allocated to 1 of 2 groups: small-group training (n = 123) or self-directed Internet-based training (n = 113). Prior to intervention delivery, all participants were given a placebo Turbuhaler and product information leaflet and received inhaler technique training based on their group. Technique was assessed following training and predictors of correct inhaler technique were examined. There was a significant improvement in the number of participants demonstrating correct technique in both groups (small group training, 12% to 63%; p training, 9% to 59%; p groups in the percent change (n = 234, p > 0.05). Increased student confidence following the intervention was a predictor for correct inhaler technique. Self-directed Internet-based training is as effective as small-group training in improving students' inhaler technique.

Evaluation and Modification of Commercial Dry Powder Inhalers for the Aerosolization of a Submicrometer Excipient Enhanced Growth (EEG) Formulation

Science.gov (United States)

Son, Yoen-Ju; Longest, P. Worth; Tian, Geng; Hindle, Michael

2013-01-01

The aim of this study was to evaluate and modify commercial dry powder inhalers (DPIs) for the aerosolization of a submicrometer excipient enhanced growth (EEG) formulation. The optimized device and formulation combination was then tested in a realistic in vitro mouth-throat - tracheobronchial (MT-TB) model. An optimized EEG submicrometer powder formulation, consisting of albuterol sulfate (drug), mannitol (hygroscopic excipient), L-leucine (dispersion enhancer) and poloxamer 188 (surfactant) in a ratio of 30:48:20:2 was prepared using a Büchi Nano spray dryer. The aerosolization performance of the EEG formulation was evaluated with 5 conventional DPIs: Aerolizer, Novolizer, HandiHaler, Exubera and Spiros. To improve powder dispersion, the HandiHaler was modified with novel mouth piece (MP) designs. The aerosol performance of each device was assessed using a next generation impactor (NGI) at airflow rates generating a pressure drop of 4 kPa across the DPI. In silico and in vitro deposition and hygroscopic growth of formulations was studied using a MT-TB airway geometry model. Both Handihaler and Aerolizer produced high emitted doses (ED) together with a significant submicrometer aerosol fraction. A modified HandiHaler with a MP including a three-dimensional (3D) array of rods (HH-3D) produced a submicrometer particle fraction of 38.8% with a conventional fine particle fraction (% <5µm) of 97.3%. The mass median diameter (MMD) of the aerosol was reduced below 1 µm using this HH-3D DPI. The aerosol generated from the modified HandiHaler increased to micrometer size (2.8 µm) suitable for pulmonary deposition, when exposed to simulated respiratory conditions, with negligible mouth-throat (MT) deposition (2.6 %). PMID:23608613

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application.

Science.gov (United States)

Kolanjiyil, Arun V; Kleinstreuer, Clement; Sadikot, Ruxana T

2017-05-01

Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of

Evaluation of a novel educational strategy, including inhaler-based reminder labels, to improve asthma inhaler technique.

Science.gov (United States)

Basheti, Iman A; Armour, Carol L; Bosnic-Anticevich, Sinthia Z; Reddel, Helen K

2008-07-01

To evaluate the feasibility, acceptability and effectiveness of a brief intervention about inhaler technique, delivered by community pharmacists to asthma patients. Thirty-one pharmacists received brief workshop education (Active: n=16, CONTROL: n=15). Active Group pharmacists were trained to assess and teach dry powder inhaler technique, using patient-centered educational tools including novel Inhaler Technique Labels. Interventions were delivered to patients at four visits over 6 months. At baseline, patients (Active: 53, CONTROL: 44) demonstrated poor inhaler technique (mean+/-S.D. score out of 9, 5.7+/-1.6). At 6 months, improvement in inhaler technique score was significantly greater in Active cf. CONTROL patients (2.8+/-1.6 cf. 0.9+/-1.4, p<0.001), and asthma severity was significantly improved (p=0.015). Qualitative responses from patients and pharmacists indicated a high level of satisfaction with the intervention and educational tools, both for their effectiveness and for their impact on the patient-pharmacist relationship. A simple feasible intervention in community pharmacies, incorporating daily reminders via Inhaler Technique Labels on inhalers, can lead to improvement in inhaler technique and asthma outcomes. Brief training modules and simple educational tools, such as Inhaler Technique Labels, can provide a low-cost and sustainable way of changing patient behavior in asthma, using community pharmacists as educators.

Development of Respimat® Soft Mist™ Inhaler and its clinical utility in respiratory disorders

Directory of Open Access Journals (Sweden)

Dalby RN

2011-09-01

Full Text Available Richard N Dalby1, Joachim Eicher2, Bernd Zierenberg21Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA; 2Boehringer Ingelheim, Ingelheim, GermanyAbstract: The Respimat® Soft Mist™ Inhaler (SMI (Boehringer Ingelheim International GmbH, Ingelheim, Germany was developed in response to the need for a pocket-sized device that can generate a single-breath, inhalable aerosol from a drug solution using a patient-independent, reproducible, and environmentally friendly energy supply. This paper describes the design and evolution of this innovative device from a laboratory concept model and the challenges that were overcome during its development and scaleup to mass production. A key technical breakthrough was the uniblock, a component combining filters and nozzles and made of silicon and glass, through which drug solution is forced using mechanical power. This allows two converging jets of solution to collide at a controlled angle, generating a fine aerosol of inhalable droplets. The mechanical energy comes from a spring which is tensioned by twisting the base of the device before use. Additional features of the Respimat® SMI include a dose indicator and a lockout mechanism to avoid the problems of tailing-off of dose size seen with pressurized metered dose inhalers. The Respimat® SMI aerosol cloud has a unique range of technical properties. The high fine particle fraction allied with the low velocity and long generation time of the aerosol translate into a higher fraction of the emitted dose being deposited in the lungs compared with aerosols from pressurized metered dose inhalers and dry powder inhalers. These advantages are realized in clinical trials in adults and children with obstructive lung diseases, which have shown that the efficacy and safety of a pressurized metered dose inhaler formulation of a combination bronchodilator can be matched by a Respimat® SMI formulation containing only one half or one quarter

Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks.

Science.gov (United States)

Muddle, Joanna; Kirton, Stewart B; Parisini, Irene; Muddle, Andrew; Murnane, Darragh; Ali, Jogoth; Brown, Marc; Page, Clive; Forbes, Ben

2017-01-01

Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory diseases, but are complex products with multivariate performance determinants. Heuristic product development guided by in vitro aerosol performance testing is a costly and time-consuming process. This study investigated the feasibility of using artificial neural networks (ANNs) to predict fine particle fraction (FPF) based on formulation device variables. Thirty-one ANN architectures were evaluated for their ability to predict experimentally determined FPF for a self-consistent dataset containing salmeterol xinafoate and salbutamol sulfate dry powder inhalers (237 experimental observations). Principal component analysis was used to identify inputs that significantly affected FPF. Orthogonal arrays (OAs) were used to design ANN architectures, optimized using the Taguchi method. The primary OA ANN r 2 values ranged between 0.46 and 0.90 and the secondary OA increased the r 2  values (0.53-0.93). The optimum ANN (9-4-1 architecture, average r 2 0.92 ± 0.02) included active pharmaceutical ingredient, formulation, and device inputs identified by principal component analysis, which reflected the recognized importance and interdependency of these factors for orally inhaled product performance. The Taguchi method was effective at identifying successful architecture with the potential for development as a useful generic inhaler ANN model, although this would require much larger datasets and more variable inputs. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Experiments to Populate and Validate a Processing Model for Polyurethane Foam: Additional Data for Structural Foams

Energy Technology Data Exchange (ETDEWEB)

Rao, Rekha R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Celina, Mathias C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Giron, Nicholas Henry [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Long, Kevin Nicholas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Russick, Edward M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-01-01

We are developing computational models to help understand manufacturing processes, final properties and aging of structural foam, polyurethane PMDI. Th e resulting model predictions of density and cure gradients from the manufacturing process will be used as input to foam heat transfer and mechanical models. BKC 44306 PMDI-10 and BKC 44307 PMDI-18 are the most prevalent foams used in structural parts. Experiments needed to parameterize models of the reaction kinetics and the equations of motion during the foam blowing stages were described for BKC 44306 PMDI-10 in the first of this report series (Mondy et al. 2014). BKC 44307 PMDI-18 is a new foam that will be used to make relatively dense structural supports via over packing. It uses a different catalyst than those in the BKC 44306 family of foams; hence, we expect that the reaction kineti cs models must be modified. Here we detail the experiments needed to characteriz e the reaction kinetics of BKC 44307 PMDI-18 and suggest parameters for the model based on these experiments. In additi on, the second part of this report describes data taken to provide input to the preliminary nonlinear visco elastic structural response model developed for BKC 44306 PMDI-10 foam. We show that the standard cu re schedule used by KCP does not fully cure the material, and, upon temperature elevation above 150°C, oxidation or decomposition reactions occur that alter the composition of the foam. These findings suggest that achieving a fully cured foam part with this formulation may be not be possible through therma l curing. As such, visco elastic characterization procedures developed for curing thermosets can provide only approximate material properties, since the state of the material continuously evolves during tests.

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

Science.gov (United States)

Kinnunen, Hanne; Hebbink, Gerald; Peters, Harry; Huck, Deborah; Makein, Lisa; Price, Robert

2015-01-15

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 (0.8 wt%) were prepared with three different lactose carriers (Lactohale (LH) LH100, 20 wt% LH210 in LH100 and 20 wt% 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 90 l/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 (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. Copyright © 2014 Elsevier B.V. All rights reserved.

A non-electrostatic spacer for aerosol delivery

DEFF Research Database (Denmark)

Bisgaard, H; Anhøj, J; Klug, B

1995-01-01

A pear shaped non-electrostatic spacer, composed of steel with a volume of 250 ml and equipped with a facemask containing integrated inlet and outlet valves for inspiration and expiration, was compared with three plastic spacers. The plastic spacers were primed with repeated puffs from a budesonide...... pressurised metered dose inhaler (p-MDI) to minimise the electrostatic charge on the plastic. The procedure prolonged the half life (t1/2) of the aerosol in the Nebuhaler from nine to 32 seconds. A normal cleaning procedure reduced the aerosol t1/2 back to baseline. The t1/2 of the aerosol in the metal spacer...... was 27 seconds and independent of the use of p-MDI. In vitro the maximum dose of budesonide from a p-MDI, expressed as a percentage of the nominal dose, was 56% from the non-electrostatic spacer, 61% from the Nebuhaler, 45% from the Babyhaler, and 30% from the AeroChamber. In 124 children, age 6 months...

Dry powder inhalation of hemin to induce heme oxygenase expression in the lung

NARCIS (Netherlands)

Zijlstra, G.S.; Brandsma, C.; Harpe, M.F.H.; Van Dam, G.M.; Slebos, D.J.; Kerstjens, H.A.M.; de Boer, Anne; Frijlink, H.W.

2007-01-01

The purpose of this study was to formulate hemin as a powder for inhalation and to show proof of concept of heme oxygenase 1 (HO-1) expression in the lungs of mice by inhalation of hemin. Hemin was spray dried from a neutralized sodium hydroxide solution. The particle size distribution of the powder

Inhaler education for hospital-based pharmacists: how much is required?

Science.gov (United States)

Jackevicius, C A; Chapman, K R

1999-01-01

To compare the effectiveness of a more intensive educational intervention with a less intensive intervention on the ability of hospital pharmacists to be prepared to educate patients regarding inhaled device technique. Randomized controlled trial. Inhaler technique and knowledge were assessed pre-education, immediately after and three months after education by a research assistant blinded to the educational allocation. Tertiary hospital pharmacy department. Hospital-based pharmacists. A 1 h 'hands-on' session with feedback (more intense education, MIE) or written materials describing inhaler use (less intense education, LIE). The change in overall score from pre-education to early posteducation for MIE was greater than for LIE (mean [95% CI]) (2.64 [1.27 to 4.01] versus 1.26 [0.05 to 2.47], PMIE group than the LIE group, a difference that was not statistically significant (1.78 [0.82 to 2.74] versus 1. 22 [0.06 to 2.39], P=0.09). Scores in both groups were lower in the late posteducation period compared with the early posteducation period. Greater increases in total score in the immediate posteducation period were associated with a low baseline score and the MIE intervention. Individual coaching in inhaler technique produces greater improvement in inhaler knowledge among hospital pharmacists than provision of written materials. However, the advantage of the more intensive intervention was short-lived, with little advantage evident in three months.

Delivery of theophylline as dry powder for inhalation

Directory of Open Access Journals (Sweden)

Bing Zhu

2015-12-01

Full Text Available Theophylline (TP is a very well established orally or intravenously delivered antiasthma drug with many beneficial effects. This study aims to improve asthma treatment by creating a dry powder inhalable (DPI formulation of TP to be delivered directly to the lung, avoiding the side effects associated with conventional oral delivery. The DPI TP formulation was investigated for its physico-chemical characteristics using scanning electron microscopy, laser diffraction, thermal analysis and dynamic vapour sorption. Furthermore, aerosol performance was assessed using the Multi Stage Liquid Impinger (MSLI. In addition, a Calu-3 cell transport assay was conducted in vitro using a modified ACI to study the impact of the DPI formulation on lung epithelial cells. Results showed DPI TP to be physico-chemically stable and of an aerodynamic size suitable for lung delivery. The aerosolisation performance analysis showed the TP DPI formulation to have a fine particle fraction of 29.70 ± 2.59% (P < 0.05 for the TP formulation containing 1.0% (w/w sodium stearate, the most efficient for aerosolisation. Regarding the deposition of TP DPI on Calu-3 cells using the modified ACI, results demonstrated that 56.14 ± 7.62% of the total TP deposited (13.07 ± 1.69 µg was transported across the Calu-3 monolayer over 180 min following deposition, while 37.05 ± 12.62% of the deposited TP was retained in the cells. This could be due to the presence of sodium stearate in the current formulation that increased its lipophilicity. A DPI formulation of TP was developed that was shown to be suitable for inhalation.

Nanomaterial inhalation exposure from nanotechnology-based cosmetic powders: a quantitative assessment

International Nuclear Information System (INIS)

Nazarenko, Yevgen; Zhen Huajun; Han Taewon; Lioy, Paul J.; Mainelis, Gediminas

2012-01-01

In this study we quantified exposures to airborne particles ranging from 14 nm to 20 μm due to the use of nanotechnology-based cosmetic powders. Three nanotechnology-based and three regular cosmetic powders were realistically applied to a mannequin’s face while measuring the concentration and size distribution of inhaled aerosol particles. Using these data we calculated that the highest inhaled particle mass was in the coarse aerosol fraction (2.5–10 μm), while particles <100 nm made minimal contribution to the inhaled particle mass. For all powders, 85–93 % of aerosol deposition occurred in the head airways, while <10 % deposited in the alveolar and <5 % in the tracheobronchial regions. Electron microscopy data suggest that nanomaterials were likely distributed as agglomerates across the entire investigated aerosol size range (14 nm–20 μm). Thus, investigation of nanoparticle health effects should consider not only the alveolar region, but also other respiratory system regions where substantial nanomaterial deposition during the actual nanotechnology-based product use would occur.

Flow Formulations for Curriculum-based Course Timetabling

DEFF Research Database (Denmark)

Bagger, Niels-Christian Fink; Kristiansen, Simon; Sørensen, Matias

2017-01-01

lower bound on one data instance in the benchmark data set from the second international timetabling competition. Regarding upper bounds, the formulation based on the minimum cost flow problem performs better on average than other mixed integer programming approaches for the CTT.......In this paper we present two mixed-integer programming formulations for the Curriculum based Course Timetabling Problem (CTT). We show that the formulations contain underlying network structures by dividing the CTT into two separate models and then connect the two models using flow formulation...... techniques. The first mixed-integer programming formulation is based on an underlying minimum cost flow problem, which decreases the number of integer variables significantly and improves the performance compared to an intuitive mixed-integer programming formulation. The second formulation is based...

Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges

Directory of Open Access Journals (Sweden)

Wing-Hin Lee

2015-12-01

Full Text Available Ever since the success of developing inhalable insulin, drug delivery via pulmonary administration has become an attractive route to treat chronic diseases. Pulmonary delivery system for nanotechnology is a relatively new concept especially when applicable to lung cancer therapy. Nano-based systems such as liposome, polymeric nanoparticles or micelles are strategically designed to enhance the therapeutic index of anti-cancer drugs through improvement of their bioavailability, stability and residency at targeted lung regions. Along with these benefits, nano-based systems also provide additional diagnostic advantages during lung cancer treatment, including imaging, screening and drug tracking. Nevertheless, delivery of nano-based drugs via pulmonary administration for lung cancer therapy is still in its infancy and numerous challenges are expected. Pharmacology, immunology, toxicology and large-scale manufacturing (stability and activity of drugs are some aspects in nanotechnology that should be taken into consideration for the development of inhalable nano-based chemotherapeutic drugs. This review will focus on the current inhalable nano-based drugs for lung cancer treatment.

Albuterol Delivery via Facial and Tracheostomy Route in a Model of a Spontaneously Breathing Child.

Science.gov (United States)

Cooper, Brandy; Berlinski, Ariel

2015-12-01

Some pediatric patients receiving therapeutic aerosols undergo tracheostomy, and others who are tracheostomized continue requiring inhaled therapies upon decannulation. It is unknown whether a dose adjustment is required. Different devices are available for facial and tracheostomy delivery, and in some instances, the assisted technique is used. We hypothesized that the change from face mask to tracheostomy would result in a decrease in the lung dose. A breathing simulator connected in series to a filter holder and an anatomically correct head model of a child was used. The drug captured in the filter was termed the lung dose. Breathing patterns with tidal volumes of 50, 155, and 300 mL were tested. Albuterol hydrofluoroalkane (pressurized metered-dose inhaler [pMDI]) with an AeroChamber Mini (face and 4.5-mm tracheostomy), AeroTrach (4.5-mm tracheostomy), and AeroChamber (face) and albuterol (2.5 mg/3 mL) with a continuous output nebulizer (face and 4.5-mm tracheostomy) were tested. Masks were used for facial delivery. Four units of each device were tested. Particle size of the pMDI was measured by cascade impaction. Albuterol concentration was determined via spectrophotometry (276 nm). Switching from facial to tracheostomy delivery increased lung dose with nebulizer (all breathing patterns). When a pMDI was used, lung dose was unchanged or increased for the 50- and 155-mL and decreased for the 300-mL breathing pattern. The use of the assisted technique increased lung dose only during nebulization with the 300-mL breathing pattern. The particle size of the pMDI decreased by 19-23% when traveling through the tracheostomy tube, which retained tracheostomy was variable and depended on the delivery device and the breathing pattern. There is no advantage of using the assisted technique to enhance aerosol delivery. Copyright © 2015 by Daedalus Enterprises.

[Inhaled treatments in cystic fibrosis: what's new in 2013?].

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Dubus, J-C; Bassinet, L; Chedevergne, F; Delaisi, B; Desmazes-Dufeu, N; Reychler, G; Vecellio, L

2014-04-01

In the past few years some new inhaled drugs and inhalation devices have been proposed for the treatment of cystic fibrosis. Breath-controlled nebulizers allow increased pulmonary deposition, with a lower variability and a shorter delivery time. The new dry powder formulations of tobramycin, colistine and mannitol require a change in the inhalation technique which must be slow and deep. In the field of the inhaled mucolytic drugs, hypertonic saline and mannitol have an indication in some patients. With regard to antibiotics, dry-powder tobramycin and colistine can be substituted for the same drug delivered by nebulization. Nebulized aztreonam needs more studies to determine its place. These new treatments represent a definite advance for cystic fibrosis patients and need to be known by all practitioners. Their position in our therapeutic arsenal remains to be accurately defined. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Formulation variables affecting deposition with the Kchaler device, a ...

African Journals Online (AJOL)

As a result of current focus on tightening regulatory requirements, it is imperative that reproducibility of the metered dose of drugs be ensured during the formulation, packaging and use. We developed a dry powder inhalation package in our laboratories consisting of formulation mixes, design and a device, KCHALER, ...

Inhaled Antibiotics for Gram-Negative Respiratory Infections

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Fraidenburg, Dustin R.; Scardina, Tonya

2016-01-01

SUMMARY Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena. PMID:27226088

Effect of different single-session educational modalities on improving medical students' ability to demonstrate proper pressurized metered dose inhaler technique.

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Dominelli, Giulio S; Dominelli, Paolo B; Rathgeber, Steven L; Webster, Sheila B

2012-05-01

Pressurized metered dose inhalers (pMDIs) remain important therapeutic options for obstructive lung diseases. The ability to instruct and evaluate inhaler technique is a crucial skill that all medical professionals should possess; unfortunately, many professionals lack proficiency with pMDIs. We aimed to determine if brief education interventions of differing modalities can positively affect medical students' skills over the long term. The baseline ability of medical students and first year residents to use pMDIs was scored via a 10-point scoring system. Students were randomized to receive no education, one-on-one instruction, or video instruction. Students were then retested immediately after the education and at the 3-month mark for retention of acquired skills. Video, one-on-one and the placebo groups modalities statistically improved the average medical student's score in the immediate retesting (7.5 and 7.4 vs. 4.7, p grades at the immediate recall significantly improved for both modalities. During retention testing, only video education had a statistically significant improvement in pass rate over the control group, as defined by an average score of 7 or better (8 vs. 1, p improve medical students' ability to use pMDIs in short-term testing. However, only video education retained significant improvement compared with control after 3 months. This suggests that compared with traditional one-on-one teaching, video education is an effective means of teaching medical students how to improve their pMDI technique.

Nanotechnology-based inhalation treatments for lung cancer: state of the art

Directory of Open Access Journals (Sweden)

Ahmad J

2015-11-01

Full Text Available Javed Ahmad,1,* Sohail Akhter,2,3,* Md Rizwanullah,1 Saima Amin,1 Mahfoozur Rahman,4 Mohammad Zaki Ahmad,5 Moshahid Alam Rizvi,6 Mohammad A Kamal,7 Farhan Jalees Ahmad1,21Department of Pharmaceutics, 2Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India; 3Centre de Biophysique Moléculaire(CBM-CNRS UPR4301, University of Orléans, Orléans Cedex 2, France; 4Department of Pharmaceutics, Abhilashi College of Pharmacy, Mandi, HP, India; 5Department of Pharmaceutics, College of Pharmacy, Najran University, Saudi Arabia; 6Department of Biosciences, Jamia Millia Islamia, New Delhi, India; 7Metabolomics and Enzymology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia*These authors contributed equally to this workAbstract: Considering the challenges associated with conventional chemotherapy, targeted and local delivery of chemotherapeutics via nanoparticle (NP carriers to the lungs is an emerging area of interest. Recent studies and growing clinical application in cancer nanotechnology showed the huge potential of NPs as drug carriers in cancer therapy, including in lung carcinoma for diagnosis, imaging, and theranostics. Researchers have confirmed that nanotechnology-based inhalation chemotherapy is viable and more effective than conventional chemotherapy, with lesser side effects. Recently, many nanocarriers have been investigated, including liposomes, polymeric micelles, polymeric NPs, solid lipid NPs, and inorganic NPs for inhalation treatments of lung cancer. Yet, the toxicity of such nanomaterials to the lungs tissues and further distribution to other organs due to systemic absorption on inhalation delivery is a debatable concern. Here, prospect of NPs-based local lung cancer targeting through inhalation route as well as its associated challenges are discussed.Keywords: nanoparticles, lung cancer, inhalational chemotherapy, drug targeting, nanotoxicity

Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer™ disposable high-dose dry powder inhaler.

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de Boer, Anne H; Hagedoorn, Paul; Woolhouse, Robert; Wynn, Ed

2012-09-01

To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high-dose disposable Twincer™ dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Comparison of predicted flow and particle behaviour from CFD computations with experimental data obtained with cascade impactor and laser diffraction analysis. Inhaler resistance, flow split, particle trajectories and particle residence times can well be predicted with CFD for a multiple classifier based inhaler like the Twincer™. CFD computations showed that the flow split of the Twincer™ is independent of the pressure drop across the inhaler and that the total flow rate can be decreased without affecting the dispersion efficacy or retention behaviour. They also showed that classifier symmetry can be improved by reducing the resistance of one of the classifier bypass channels, which for the current concept does not contribute to the swirl in the classifier chamber. CFD is a highly valuable tool for development and optimisation of dry powder inhalers. CFD can assist adapting the inhaler design to specific physico-chemical properties of the drug formulation with respect to dispersion and retention behaviour. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

A Systematic Analysis of the Sensitivity of Plasma Pharmacokinetics to Detect Differences in the Pulmonary Performance of Inhaled Fluticasone Propionate Products Using a Model-Based Simulation Approach.

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Weber, Benjamin; Hochhaus, Guenther

2015-07-01

The role of plasma pharmacokinetics (PK) for assessing bioequivalence at the target site, the lung, for orally inhaled drugs remains unclear. A validated semi-mechanistic model, considering the presence of mucociliary clearance in central lung regions, was expanded for quantifying the sensitivity of PK studies in detecting differences in the pulmonary performance (total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics) between test (T) and reference (R) inhaled fluticasone propionate (FP) products. PK bioequivalence trials for inhaled FP were simulated based on this PK model for a varying number of subjects and T products. The statistical power to conclude bioequivalence when T and R products are identical was demonstrated to be 90% for approximately 50 subjects. Furthermore, the simulations demonstrated that PK metrics (area under the concentration time curve (AUC) and C max) are capable of detecting differences between T and R formulations of inhaled FP products when the products differ by more than 20%, 30%, and 25% for total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics, respectively. These results were derived using a rather conservative risk assessment approach with an error rate of <10%. The simulations thus indicated that PK studies might be a viable alternative to clinical studies comparing pulmonary efficacy biomarkers for slowly dissolving inhaled drugs. PK trials for pulmonary efficacy equivalence testing should be complemented by in vitro studies to avoid false positive bioequivalence assessments that are theoretically possible for some specific scenarios. Moreover, a user-friendly web application for simulating such PK equivalence trials with inhaled FP is provided.

Estimation of chloroform inhalation dose by other routes based on the relationship of area under the blood concentration-time curve (AUC)-inhalation dose to chloroform distribution in the blood of rats.

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Take, Makoto; Takeuchi, Tetsuya; Haresaku, Mitsuru; Matsumoto, Michiharu; Nagano, Kasuke; Yamamoto, Seigo; Takamura-Enya, Takeji; Fukushima, Shoji

2014-01-01

The present study investigated the time-course changes of concentration of chloroform (CHCl3) in the blood during and after exposure of male rats to CHCl3 by inhalation. Increasing the dose of CHCl3 in the inhalation exposed groups caused a commensurate increase in the concentration of CHCl3 in the blood and the area under the blood concentration-time curve (AUC). There was good correlation (r = 0.988) between the inhalation dose and the AUC/kg body weight. Based on the AUC/kg body weight-inhalation dose curve and the AUC/kg body weight after oral administration, inhalation equivalent doses of orally administered CHCl3 were calculated. Calculation of inhalation equivalent doses allows the body burden due to CHCl3 by inhalation exposure and oral exposure to be directly compared. This type of comparison facilitates risk assessment in humans exposed to CHCl3 by different routes. Our results indicate that when calculating inhalation equivalent doses of CHCl3, it is critical to include the AUC from the exposure period in addition to the AUC after the end of the exposure period. Thus, studies which measure the concentration of volatile organic compounds in the blood during the inhalation exposure period are crucial. The data reported here makes an important contribution to the physiologically based pharmacokinetic (PBPK) database of CHCl3 in rodents.

Effect of Pressurized Metered Dose Inhaler Spray Characteristics and Particle Size Distribution on Drug Delivery Efficiency.

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Yousefi, Morteza; Inthavong, Kiao; Tu, Jiyuan

2017-10-01

A key issue in pulmonary drug delivery is improvement of the delivery device for effective and targeted treatment. Pressurized metered dose inhalers (pMDIs) are the most popular aerosol therapy device for treating lung diseases. This article studies the effect of spray characteristics: injection velocity, spray cone angle, particle size distribution (PSD), and its mass median aerodynamic diameter (MMAD) on drug delivery. An idealized oral airway geometry, extending from mouth to the main bronchus, was connected to a pMDI device. Inhalation flow rates of 15, 30, and 60 L/min were used and drug particle tracking was a one-way coupled Lagrangian model. The results showed that most particles deposited in the pharynx, where the airway has a reduced cross-sectional area. Particle deposition generally decreased with initial spray velocity and with increased spray cone angle for 30 and 60 L/min flow rates. However, for 15 L/min flow rate, the deposition increased slightly with an increase in the spray velocity and cone angle. The effect of spray cone angle was more significant than the initial spray velocity on particle deposition. When the MMAD of a PSD was reduced, the deposition efficiency also reduces, suggesting greater rates of particle entry into the lung. The deposition rate showed negligible change when the MMAD was more than 8 μm. Spray injection angle and velocity change the drug delivery efficacy; however, the efficiency shows more sensitivity to the injection angle. The 30 L/min airflow rate delivers spray particles to the lung more efficiently than 15 and 60 L/min airflow rate, and reducing MMAD can help increase drug delivery to the lung.

Dispersing the Mists: An Experimental History of Medicine Study into the Quality of Volatile Inhalations.

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Murnane, Barry; Gallagher, Cathal T; Snell, Noel; Sanders, Mark; Moshksar, Ramin; Murnane, Darragh

2017-06-01

Dr. Nelson's Improved Inhaler was first marketed with an advertisement in The Lancet in 1865. Revolutionary at the time for its ease of use and patient-friendliness, the inhaler is still in use for self-treatment by many all over the world. On the occasion of its 150th anniversary, this study reports an experimental historical medicine approach to identify evidence for the quality of vapor inhalers. Through accessing reviews of the device's use by the contemporary medical establishment, it was established that Dr. Nelson's Inhaler enjoyed a reputation of quality and efficacy among reputable physicians generating empirical evidence of clinical performance. There was a general absence of product performance tests during this period. Therefore, modern inhalation performance testing was applied to test the aerosol delivery performance for Friars' Balsam, and its key chemical constituent, benzoic acid (BA). A respirable dose of 59.9 ± 9.0 μg of BA was aerosolized in a 10 minutes period from a dose of 3.3 mL Friars' Balsam (equivalent to 35.1 ± 0.2 mg of BA) in 375 mL of steaming water using the glass twin stage impinger at a flow rate of 60 L·min -1 . The respirable dose from a standardized aqueous BA inhalation formulation increased from 115.9 ± 10.6 to 200.2 ± 19.9 μg by increasing the simulated inhalation period from 5 to 10 minutes. When tested with a simulated inhalation maneuver (500 mL tidal volume, 13 minutes -1 respiration rate, 1:2 inspiratory:expiratory ratio) a respirable dose of 112.8 ± 40.3 μg was produced. This work has highlighted the potential for aerosol drug delivery using steam inhalers that are popular with patients. Physicians should therefore be aware of the potential for lung dosing with irritants when patients self-medicate using the Nelson Inhaler with vaporizing formulations such as Friars' Balsam.

In vitro tests for aerosol deposition. III: effect of inhaler insertion angle on aerosol deposition.

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Delvadia, Renish R; Longest, P Worth; Hindle, Michael; Byron, Peter R

2013-06-01

Inhaler orientation with respect to a patient's mouth may be an important variable determining the efficiency of aerosol lung delivery. The effect of insertion angle on regional deposition was evaluated for a series of inhalers using concurrent in vitro and computational fluid dynamics (CFD) analysis. Geometrically realistic physical mouth-throat (MT) and upper tracheobronchial (TB) models were constructed to connect different inhalers at a series of insertion angles relative to the horizontal plane of the model. These models were used to assess albuterol sulfate deposition from the Novolizer(®) dry powder inhaler (DPI), Proventil(®) HFA pressurized metered dose inhaler (MDI), and Respimat(®) Soft Mist™ Inhaler (SMI) following the actuation of a single dose. Drug deposition from Novolizer DPI was studied for Salbulin(®) and an experimental "drug only" formulation. Albuterol sulfate was recovered and quantified from the device and the MT and TB regions. Significant differences in MT and total lung dose (TLD) of albuterol sulfate deposition were not observed for Salbulin Novolizer DPI and Respimat SMI inserted at different angles. In contrast, drug-only Novolizer DPI and Proventil HFA MDI showed a significant difference in MT and TLD deposition using different insertion angles. For drug-only Novolizer DPI and Proventil HFA MDI, the lowest and the highest MT depositions were observed at +10° and -20°, respectively; for Respimat SMI and Salbulin Novolizer DPI, these angles were -10° and +10°, and +20° and -20°, respectively. CFD simulations were in agreement with the experimental results and illustrated shifts in local particle deposition associated with changes in insertion angle. The effect of inhaler orientation at the inhaler-mouth interface on MT aerosol deposition appeared to be dependent on velocity, aerosol size, and formulation. These findings not only demonstrate the need for patient education on correct inhaler orientation, but provide important

Objective measurement of inhaler inhalation flow profile using acoustic methods

Energy Technology Data Exchange (ETDEWEB)

Lacalle, H.; Taylor, T.E.; Marco, S.; Reilly, R.B.

2016-07-01

Patients with asthma and chronic obstructive pulmonary diseases (COPD) are mostly treated with inhalers that deliver medication directly to their airways. Drug delivery from dry powder inhalers (DPIs) is very much reliant on the inhalation manoeuvre, specifically the peak inspiratory flow rate (PIFR), inspiratory capacity (IC) and inhalation rise time (IRT) of the inhalation. It has been widely reported that patients may not follow correct inhalation technique while using their inhaler. In this study, a novel acoustic method is proposed to accurately estimate inhalation flow profile using only one inhalation recording for calibration. An Ellipta DPI was placed inside an airtight container with a spirometer connected in order to measure inhalation flow parameters. An acoustic recording device (Inhaler Compliance Assessment (INCA)) was also attached to the DPI. Inhalation audio and flow signals were recorded simultaneously. The data were collected from 20 healthy subjects while performing inhaler inhalations at a range of inspiratory flow rates. A power law regression model was computed to obtain the relationship between the acoustic envelope of the inhalation and flow profile of each recording. Each model was tested on the remaining audio signals to estimate flow profile. The average estimation error was found to be 10.5±0.3% for estimating flow profile from audio signals. Inhalation flow profile parameters (PIFR, IC and IRT) could then be measured from the estimated flow profile with high accuracy giving information on user inhalation technique. This method may assist in improving patient inhaler adherence and overall disease control. (Author)

An Acoustic-Based Method to Detect and Quantify the Effect of Exhalation into a Dry Powder Inhaler.

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Holmes, Martin S; Seheult, Jansen N; O'Connell, Peter; D'Arcy, Shona; Ehrhardt, Carsten; Healy, Anne Marie; Costello, Richard W; Reilly, Richard B

2015-08-01

Dry powder inhaler (DPI) users frequently exhale into their inhaler mouthpiece before the inhalation step. This error in technique compromises the integrity of the drug and results in poor bronchodilation. This study investigated the effect of four exhalation factors (exhalation flow rate, distance from mouth to inhaler, exhalation duration, and relative air humidity) on dry powder dose delivery. Given that acoustic energy can be related to the factors associated with exhalation sounds, we then aimed to develop a method of identifying and quantifying this critical inhaler technique error using acoustic based methods. An in vitro test rig was developed to simulate this critical error. The effect of the four factors on subsequent drug delivery were investigated using multivariate regression models. In a further study we then used an acoustic monitoring device to unobtrusively record the sounds 22 asthmatic patients made whilst using a Diskus(™) DPI. Acoustic energy was employed to automatically detect and analyze exhalation events in the audio files. All exhalation factors had a statistically significant effect on drug delivery (pacoustic method detected exhalations with an accuracy of 89.1%. We were able to classify exhalations occurring 5 cm or less in the direction of the inhaler mouthpiece or recording device with a sensitivity of 72.2% and specificity of 85.7%. Exhaling into a DPI has a significant detrimental effect. Acoustic based methods can be employed to objectively detect and analyze exhalations during inhaler use, thus providing a method of remotely monitoring inhaler technique and providing personalized inhaler technique feedback.

Preparation and Evaluation of Surface Modified Lactose Particles for Improved Performance of Fluticasone Propionate Dry Powder Inhaler.

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Singh, Deepak J; Jain, Rajesh R; Soni, P S; Abdul, Samad; Darshana, Hegde; Gaikwad, Rajiv V; Menon, Mala D

2015-08-01

Dry powder inhalers (DPI) are generally formulated by mixing micronized drug particles with coarse lactose carrier particles to assist powder handling during the manufacturing and powder aerosol delivery during patient use. In the present study, surface modified lactose (SML) particles were produced using force control agents, and their in vitro performance on dry powder inhaler (DPI) formulation of Fluticasone propionate was studied. With a view to reduce surface passivation of high surface free energy sites on the most commonly used DPI carrier, α- lactose monohydrate, effects of various force control agents such as Pluronic F-68, Cremophor RH 40, glyceryl monostearate, polyethylene glycol 6000, magnesium stearate, and soya lecithin were studied. DPI formulations prepared with SML showed improved flow properties, and atomic force microscopy (AFM) studies revealed decrease in surface roughness. The DSC and X-ray diffraction patterns of SML showed no change in the crystal structure and thermal behavior under the experimental conditions. The fine particle fraction (FPF) values of lactose modified with Pluronic F-68, Cremophor RH 40, glyceryl monostearate were improved, with increase in concentration up to 0.5%. Soya lecithin and PEG 6000 modified lactose showed decrease in FPF value with increase in concentration. Increase in FPF value was observed with increasing concentration of magnesium stearate. Two different DPI devices, Rotahaler(®) and Diskhaler(®), were compared to evaluate the performance of SML formulations. FPF value of all SML formulations were higher using both devices as compared to the same formulations prepared using untreated lactose. One month stability of SML formulations at 40°C/75% RH, in permeable polystyrene tubes did not reveal any significant changes in FPF values. SML particles can help in reducing product development hindrances and improve inhalational properties of DPI.

The effect of ethanol on the formation and physico-chemical properties of particles generated from budesonide solution-based pressurized metered-dose inhalers.

Science.gov (United States)

Zhu, Bing; Traini, Daniela; Chan, Hak-Kim; Young, Paul M

2013-11-01

The aerosol performance of budesonide solution-based pressurized metered-dose inhalers (HFA 134a), with various amounts of ethanol (5-30%, w/w) as co-solvents, was evaluated using impaction and laser diffraction techniques. With the increase of ethanol concentration in a formulation, the mass median aerodynamic diameter was increased and the fine particle fraction showed a significant decline. Although data obtained from laser diffraction oversized that of the impaction measurements, good correlations were established between the two sets of data. Particles emitted from all the five formulations in this study were amorphous, with two different types of morphology - the majority had a smooth surface with a solid core and the others were internally porous with coral-like surface morphology. The addition of ethanol in the formulation decreased the percentage of such irregular-shape particles from 52% to 2.5% approximately, when the ethanol concentration was increased from 5% to 30%, respectively. A hypothesis regarding the possible particle formation mechanisms was also established. Due to the difference of droplet composition from the designed formulation during the atomization process, the two types of particle may have gone through distinct drying processes: both droplets will have a very short period of co-evaporation, droplets with less ethanol may be dried during such period; while the droplets containing more ethanol will undergo an extra condensation stage before the final particle formation.

Towards the optimisation and adaptation of dry powder inhalers.

Science.gov (United States)

Cui, Y; Schmalfuß, S; Zellnitz, S; Sommerfeld, M; Urbanetz, N

2014-08-15

Pulmonary drug delivery by dry powder inhalers is becoming more and more popular. Such an inhalation device must insure that during the inhalation process the drug powder is detached from the carrier due to fluid flow stresses. The goal of the project is the development of a drug powder detachment model to be used in numerical computations (CFD, computational fluid dynamics) of fluid flow and carrier particle motion through the inhaler and the resulting efficiency of drug delivery. This programme will be the basis for the optimisation of inhaler geometry and dry powder inhaler formulation. For this purpose a multi-scale approach is adopted. First the flow field through the inhaler is numerically calculated with OpenFOAM(®) and the flow stresses experienced by the carrier particles are recorded. This information is used for micro-scale simulations using the Lattice-Boltzmann method where only one carrier particle covered with drug powder is placed in cubic flow domain and exposed to the relevant flow situations, e.g. plug and shear flow with different Reynolds numbers. Therefrom the fluid forces on the drug particles are obtained. In order to allow the determination of the drug particle detachment possibility by lift-off, sliding or rolling, also measurements by AFM (atomic force microscope) were conducted for different carrier particle surface structures. The contact properties, such as van der Waals force, friction coefficient and adhesion surface energy were used to determine, from a force or moment balance (fluid forces versus contact forces), the detachment probability by the three mechanisms as a function of carrier particle Reynolds number. These results will be used for deriving the drug powder detachment model. Copyright © 2014 Elsevier B.V. All rights reserved.

Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

Science.gov (United States)

Zarogouldis, Paul; Karamanos, Nikos K.; Porpodis, Konstantinos; Domvri, Kalliopi; Huang, Haidong; Hohenforst-Schimdt, Wolfgang; Goldberg, Eugene P.; Zarogoulidis, Konstantinos

2012-01-01

Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer. PMID:23109824

Inhaled Steroids

Science.gov (United States)

... considerations when your dosage changes. What about side effects and inhaled steroids? The most common side effects with inhaled steroids ... inhaled steroid has much less potential for side effects than steroid pills or syrups. There have been concerns regarding ...

Inhalant Abuse

Science.gov (United States)

... is when you pour the product into a bag, hold it over your mouth and nose, and inhale. How is inhalant abuse diagnosed? If you think your child is abusing inhalants, talk to them. Be honest and open. Tell them ...

Applications of lipid based formulation technologies in the delivery of biotechnology-based therapeutics.

Science.gov (United States)

du Plessis, Lissinda H; Marais, Etienne B; Mohammed, Faruq; Kotzé, Awie F

2014-01-01

In the last decades several new biotechnologically-based therapeutics have been developed due to progress in genetic engineering. A growing challenge facing pharmaceutical scientists is formulating these compounds into oral dosage forms with adequate bioavailability. An increasingly popular approach to formulate biotechnology-based therapeutics is the use of lipid based formulation technologies. This review highlights the importance of lipid based drug delivery systems in the formulation of oral biotechnology based therapeutics including peptides, proteins, DNA, siRNA and vaccines. The different production procedures used to achieve high encapsulation efficiencies of the bioactives are discussed, as well as the factors influencing the choice of excipient. Lipid based colloidal drug delivery systems including liposomes and solid lipid nanoparticles are reviewed with a focus on recent advances and updates. We further describe microemulsions and self-emulsifying drug delivery systems and recent findings on bioactive delivery. We conclude the review with a few examples on novel lipid based formulation technologies.

Inhalant abuse: monitoring trends by using poison control data, 1993-2008.

Science.gov (United States)

Marsolek, Melinda R; White, Nicole C; Litovitz, Toby L

2010-05-01

To demonstrate the value of poison control data as an adjunct to national drug abuse surveys and a source of data to inform and focus prevention efforts. National Poison Data System (NPDS) data are collected and compiled in real time by the 60 US poison centers as callers seek guidance for poison exposures. Demographic, geographic, product, outcome, and treatment-site data for the 35453 inhalant cases reported between 1993 and 2008 were analyzed. The prevalence of inhalant cases reported to US poison control centers decreased 33% from 1993 to 2008. Prevalence was highest among children aged 12 to 17 years and peaked in 14-year-olds. In contrast to national survey data showing nearly equal use of inhalants by both genders, 73.5% of NPDS inhalant cases occurred in boys, which suggests that boys may pursue riskier usage behaviors. Most cases (67.8%) were managed in health care facilities. More than 3400 different products were reported. Propellants, gasoline, and paint were the most frequent product categories. Propellants were the only product category that substantially increased over time. Butane, propane, and air fresheners had the highest fatality rates. Prevalence for all inhalants was highest in western mountain states and West Virginia, but geographic distribution varied according to product type. Gasoline was a proportionately greater problem for younger children; propellants were an issue for older children. NPDS should be used to monitor inhalant abuse because it provides unique, timely, and clinically useful information on medical outcomes experienced by users, includes detailed product information (brand and formulation), and can potentially be used to identify real-time demographic, geographic, and product trends. Focusing inhalant prevention efforts on the most hazardous products and most seriously affected users may improve and facilitate strategic prevention, enabling interventions such as targeted education, product reformulation, repackaging

Equivalência farmacêutica da formulação combinada de budesonida e formoterol em cápsula única com dispositivo inalador de pó Pharmaceutical equivalence of the combination formulation of budesonide and formoterol in a single capsule with a dry powder inhaler

Directory of Open Access Journals (Sweden)

Marina Andrade-Lima

2012-12-01

Full Text Available OBJETIVO: Avaliar a equivalência farmacêutica da formulação teste (associação fixa de budesonida e fumarato de formoterol em cápsula única dispensada com o dispositivo Aerocaps® em relação a uma formulação referência (budesonida e fumarato de formoterol em duas cápsulas distintas dispensadas com o dispositivo Aerolizer®. MÉTODOS: Estudo in vitro no qual foram realizadas identificação/quantificação dos ingredientes ativos por HPCL e determinação da uniformidade da dose liberada e da distribuição aerodinâmica das partículas das formulações teste e referência. RESULTADOS: Na formulação teste, o teor de budesonida e de formoterol foi de 111,0% e 103,8%, respectivamente, enquanto esse foi de 110,5% e 104,5% na formulação referência. Na formulação teste, a uniformidade das doses de budesonida e de formoterol foi de 293,2 µg e 10,2 µg, respectivamente, enquanto essa foi de 353,0 µg e 11,1 µg na formulação referência. Esses resultados estão dentro da faixa recomendada para esse tipo de formulação (75-125% da dose rotulada. A fração de partículas finas (OBJECTIVE: To evaluate the pharmaceutical equivalence of a test formulation (fixed-dose combination of budesonide and formoterol fumarate in a single capsule dispensed in an Aerocaps® inhaler in relation to a reference formulation (budesonide and formoterol fumarate in two separate capsules dispensed in an Aerolizer® inhaler. METHODS: This was an in vitro study in which we performed the identification/quantification of the active ingredients by HPLC and determined dose uniformity and aerodynamic particle size distribution in the test and reference formulations. RESULTS: In the test formulation, the content of budesonide and formoterol was 111.0% and 103.8%, respectively, compared with 110.5% and 104.5%, respectively, in the reference formulation. In the test formulation, dose uniformity regarding budesonide and formoterol was 293.2 µg and 10.2 µg

GHS additivity formula: can it predict the acute systemic toxicity of agrochemical formulations that contain acutely toxic ingredients?

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Van Cott, Andrew; Hastings, Charles E; Landsiedel, Robert; Kolle, Susanne; Stinchcombe, Stefan

2018-02-01

In vivo acute systemic testing is a regulatory requirement for agrochemical formulations. GHS specifies an alternative computational approach (GHS additivity formula) for calculating the acute toxicity of mixtures. We collected acute systemic toxicity data from formulations that contained one of several acutely-toxic active ingredients. The resulting acute data set includes 210 formulations tested for oral toxicity, 128 formulations tested for inhalation toxicity and 31 formulations tested for dermal toxicity. The GHS additivity formula was applied to each of these formulations and compared with the experimental in vivo result. In the acute oral assay, the GHS additivity formula misclassified 110 formulations using the GHS classification criteria (48% accuracy) and 119 formulations using the USEPA classification criteria (43% accuracy). With acute inhalation, the GHS additivity formula misclassified 50 formulations using the GHS classification criteria (61% accuracy) and 34 formulations using the USEPA classification criteria (73% accuracy). For acute dermal toxicity, the GHS additivity formula misclassified 16 formulations using the GHS classification criteria (48% accuracy) and 20 formulations using the USEPA classification criteria (36% accuracy). This data indicates the acute systemic toxicity of many formulations is not the sum of the ingredients' toxicity (additivity); but rather, ingredients in a formulation can interact to result in lower or higher toxicity than predicted by the GHS additivity formula. Copyright © 2018 Elsevier Inc. All rights reserved.

Microsphere based improved sunscreen formulation of ethylhexyl methoxycinnamate.

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Gogna, Deepak; Jain, Sunil K; Yadav, Awesh K; Agrawal, G P

2007-04-01

Polymethylmethacrylate (PMMA) microspheres of ethylhexyl methoxycinnamate (EHM) were prepared by emulsion solvent evaporation method to improve its photostability and effectiveness as sunscreening agent. Process parameters like stirring speed and aqueous polyvinyl alcohol (PVA) concentration were analyzed in order to optimize the formulations. Shape and surface morphology of the microspheres were examined using scanning electron microscopy. Particle size of the microspheres was determined using laser diffraction particle size analyzer. The PMMA microspheres of EHM were incorporated in water-removable cream base. The in vitro drug release of EHM in pH 7.4 was performed using dialysis membrane. Thin layer chromatography was performed to determine photostability of EHM inside the microspheres. The formulations were evaluated for sun protection factor (SPF) and minimum erythema dose (MED) in albino rats. Cream base formulation containing microspheres prepared using EHM:PMMA in ratio of 1:3 (C(3)) showed slowest drug (EHM) release and those prepared with EHM: PMMA in ratio of 1:1 showed fastest release. The cream base formulations containing EHM loaded microspheres had shown better SPF (more than 16.0) as compared to formulation C(d) that contained 3% free EHM as sunscreen agent and showed SPF 4.66. These studies revealed that the incorporation of EHM loaded PMMA microspheres into cream base had greatly increased the efficacy of sunscreen formulation approximately four times. Further, photostability was also shown to be improved in PMMA microspheres.

Humidity affects the morphology of particles emitted from beclomethasone dipropionate pressurized metered dose inhalers.

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Ivey, James W; Bhambri, Pallavi; Church, Tanya K; Lewis, David A; McDermott, Mark T; Elbayomy, Shereen; Finlay, Warren H; Vehring, Reinhard

2017-03-30

The effects of propellant type, cosolvent content, and air humidity on the morphology and solid phase of the particles produced from solution pressurized metered dose inhalers containing the corticosteroid beclomethasone dipropionate were investigated. The active ingredient was dissolved in the HFA propellants 134a and 227ea with varying levels of the cosolvent ethanol and filled into pressurized metered dose inhalers. Inhalers were actuated into an evaporation chamber under controlled temperature and humidity conditions and sampled using a single nozzle, single stage inertial impactor. Particle morphology was assessed qualitatively using field emission scanning electron microscopy and focused ion beam-helium ion microscopy. Drug solid phase was assessed using Raman microscopy. The relative humidity of the air during inhaler actuation was found to have a strong effect on the particle morphology, with solid spheroidal particles produced in dry air and highly porous particles produced at higher humidity levels. Air humidification was found to have no effect on the solid phase of the drug particles, which was predominantly amorphous for all tested formulations. A critical level of air relative humidity was required to generate porous particles for each tested formulation. This critical relative humidity was found to depend on the amount of ethanol used in the inhaler, but not on the type of propellant utilized. The results indicate that under the right circumstances water vapor saturation followed by nucleated water condensation or ice deposition occurs during particle formation from evaporating propellant-cosolvent-BDP droplets. This finding reveals the importance of condensed water or ice as a templating agent for porosity when particle formation occurs at saturated conditions, with possible implications on the pharmacokinetics of solution pMDIs and potential applications in particle engineering for drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Olodaterol Oral Inhalation

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... in a class of medications called long-acting beta-agonists (LABAs). It works by relaxing and opening ... the inhaler upright with the yellow cap closed. Turn the clear base in the direction of the ...

DNA/RNA-based formulations for treatment of breast cancer.

Science.gov (United States)

Xie, Zhaolu; Zeng, Xianghui

2017-12-01

To develop a successful formulation for the gene therapy of breast cancer, an effective therapeutic nucleic acid and a proper delivery system are essential. Increased understanding of breast cancer, and developments in biotechnology, material science and nanotechnology have provided a major impetus in the development of effective formulations for the gene therapy of breast cancer. Areas covered: We discuss DNA/RNA-based formulations that can inhibit the growth of breast cancer cells and control the progress of breast cancer. Targets for the gene therapy of breast cancer, DNA/RNA-based therapeutics and delivery systems are summarized. And examples of successful DNA/RNA-based formulations for breast cancer gene therapy are reviewed. Expert opinion: Several challenges remain in developing effective DNA/RNA-based formulations for treatment of breast cancer. Firstly, most of the currently utilized targets are not effective enough as monotherapy for breast cancer. Secondly, the requirements for co-delivery system make the preparation of formulation more complicated. Thirdly, nanoparticles with the modification of tumor-targeting ligands could be more unstable in circulation and normal tissues. Lastly, immune responses against the viral vectors are unfavorable for the gene therapy of breast cancer because of the damage to the host and the impaired therapeutic ability.

Inhaler Education for Hospital-Based Pharmacists: How Much Is Required?

OpenAIRE

Cynthia Anne Jackevicius; Kenneth R Chapman

1999-01-01

OBJECTIVE: To compare the effectiveness of a more intensive educational intervention with a less intensive intervention on the ability of hospital pharmacists to be prepared to educate patients regarding inhaled device technique.DESIGN: Randomized controlled trial. Inhaler technique and knowledge were assessed pre-education, immediately after and three months after education by a research assistant blinded to the educational allocation.SETTING: Tertiary hospital pharmacy department.POPULATION...

Inhalation Therapy in Horses.

Science.gov (United States)

Cha, Mandy L; Costa, Lais R R

2017-04-01

This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

A displacement based FE formulation for steady state problems

NARCIS (Netherlands)

Yu, Y.

2005-01-01

In this thesis a new displacement based formulation is developed for elasto-plastic deformations in steady state problems. In this formulation the displacements are the primary variables, which is in contrast to the more common formulations in terms of the velocities as the primary variables. In a

Effect of expansion chamber geometry on atomization and spray dispersion characters of a flashing mixture containing inerts. Part I. Numerical predictions and dual laser measurements.

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Ju, Dehao; Shrimpton, John; Bowdrey, Moira; Hearn, Alex

2012-08-01

A cigarette alternative is designed to deliver a dose of medicinal nicotine within a timeframe comparable to that of a cigarette, and gives much of what smokers expect from a cigarette without the risks of smoking tobacco. The design concept is the same as a pressurized metered dose inhaler (pMDI), but is a breath actuated device (Oxette(®)). This work predicts the residual mass median diameter (MMD) of the spray issuing from early stage Oxette(®) prototypes by using an evaporation model of multi-component liquid droplets with the help of a numerical multi-component two-phase actuation model (developed by the authors) to quantify the sprays. Two different formulations with 95% and 98% mass fraction of HFA 134a, and two prototypes of cigarette alternatives with different expansion chamber volumes have been analyzed by the numerical model and compared with laser based measurements. The later designed device provides a larger expansion chamber volume to enhance the propellant evaporation, recirculation, bubble generation and growth inside the chamber, and it makes a significant improvement to produce finer sprays than the earlier design. The mass fraction of the formulation does not affect significantly on the initial MMD of the droplets near the discharge orifice. However, it influences the residual MMD at x=100mm from the discharge orifice, where the ratio of the predicted residual MMDs of the droplets generated by the formulations with 98% and 95% of HFA 134a is 0.73. Although the formulation with 98% of HFA 134a can generate smaller droplets, the formulation with 95% of HFA 134a produces more steady puffs with relatively low mass flow rate. Copyright © 2012 Elsevier B.V. All rights reserved.

Inhalational Gentamicin Treatment Is Effective Against Pneumonic Plague in a Mouse Model

Directory of Open Access Journals (Sweden)

David Gur

2018-04-01

Full Text Available Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis, is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset. However, the non-specific “flu-like” symptoms often lead to delayed diagnosis and therapy. In this study, we evaluated inhalational gentamicin therapy in an infected mouse model as a means to improve antibiotic treatment efficacy. Inhalation is an attractive route for treating lung infections. The advantages include directly dosing the main infection site, the relative accessibility for administration and the lack of extensive enzymatic drug degradation machinery. In this study, we show that inhalational gentamicin treatment administered 24 h post-infection, prior to the appearance of symptoms, protected against lethal intranasal challenge with the fully virulent Y. pestis Kimberley53 strain (Kim53. Similarly, a high survival rate was demonstrated in mice treated by inhalation with another aminoglycoside, tobramycin, for which an FDA-approved inhaled formulation is clinically available for cystic fibrosis patients. Inhalational treatment with gentamicin 48 h post-infection (to symptomatic mice was also successful against a Y. pestis challenge dose of 10 i.n.LD50. Whole-body imaging using IVIS technology demonstrated that adding inhalational gentamicin to parenteral therapy accelerated the clearance of Y. pestis from the lungs of infected animals. This may reduce disease severity and the risk of secondary infections. In conclusion, our data suggest that inhalational therapy with aerosolized gentamicin may be an effective prophylactic treatment against pneumonic plague. We also demonstrate the benefit of combining this treatment with a conventional parenteral

Air classifier technology (ACT) in dry powder inhalation. Part 1 : Introduction of a novel force distribution concept (FDC) explaining the performance of a basic air classifier on adhesive mixtures

NARCIS (Netherlands)

de Boer, A H; Hagedoorn, P; Gjaltema, D; Goede, J; Frijlink, H W

2003-01-01

Air classifier technology (ACT) is introduced as part of formulation integrated dry powder inhaler development (FIDPI) to optimise the de-agglomeration of inhalation powders. Carrier retention and de-agglomeration results obtained with a basic classifier concept are discussed. The theoretical

Evaluation of metered dose inhaler spray velocities using phase Doppler anemometry (PDA).

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Liu, Xiaofei; Doub, William H; Guo, Changning

2012-02-28

Droplet velocity is an important parameter which can significantly influence inhalation drug delivery performance. Together with the droplet size, this parameter determines the efficiency of the deposition of MDI products at different sites within the lungs. In this study, phase Doppler anemometry (PDA) was used to investigate the instantaneous droplet velocity emitted from MDIs as well as the corresponding droplet size distribution. The nine commercial MDI products surveyed showed significantly different droplet velocities, indicating that droplet velocity could be used as a discriminating parameter for in vitro testing of MDI products. The droplet velocity for all tested MDI products decreased when the testing distance was increased from 3 cm to 6 cm from the front of mouthpiece, with CFC formulations showing a larger decrease than HFA formulations. The mean droplet diameters of the nine MDIs were also significantly different from one-another. Droplet size measurements made using PDA (a number-based technique) could not be directly compared to results obtained using laser light scattering measurements (a volume-based technique). This work demonstrates that PDA can provide unique information useful for characterizing MDI aerosol plumes and evaluating MDI drug delivery efficiency. PDA could also aid the evaluation of in vitro equivalence in support of formulation or manufacturing changes and in evaluation of abbreviated new drug applications (ANDAs) for MDIs. Published by Elsevier B.V.

Inhalants in Peru.

Science.gov (United States)

Lerner, R; Ferrando, D

1995-01-01

In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

Mixing time effects on the dispersion performance of adhesive mixtures for inhalation.

Directory of Open Access Journals (Sweden)

Floris Grasmeijer

Full Text Available This paper deals with the effects of mixing time on the homogeneity and dispersion performance of adhesive mixtures for inhalation. Interactions between these effects and the carrier size fraction, the type of drug and the inhalation flow rate were studied. Furthermore, it was examined whether or not changes in the dispersion performance as a result of prolonged mixing can be explained with a balance of three processes that occur during mixing, knowing drug redistribution over the lactose carrier; (de- agglomeration of the drug (and fine lactose particles; and compression of the drug particles onto the carrier surface. For this purpose, mixtures containing salmeterol xinafoate or fluticasone propionate were mixed for different periods of time with a fine or coarse crystalline lactose carrier in a Turbula mixer. Drug detachment experiments were performed using a classifier based inhaler at different flow rates. Scanning electron microscopy and laser diffraction techniques were used to measure drug distribution and agglomeration, whereas changes in the apparent solubility were measured as a means to monitor the degree of mechanical stress imparted on the drug particles. No clear trend between mixing time and content uniformity was observed. Quantitative and qualitative interactions between the effect of mixing time on drug detachment and the type of drug, the carrier size fraction and the flow rate were measured, which could be explained with the three processes mentioned. Generally, prolonged mixing caused drug detachment to decrease, with the strongest decline occurring in the first 120 minutes of mixing. For the most cohesive drug (salmeterol and the coarse carrier, agglomerate formation seemed to dominate the overall effect of mixing time at a low inhalation flow rate, causing drug detachment to increase with prolonged mixing. The optimal mixing time will thus depend on the formulation purpose and the choice for other, interacting variables.

Mixing Time Effects on the Dispersion Performance of Adhesive Mixtures for Inhalation

Science.gov (United States)

Grasmeijer, Floris; Hagedoorn, Paul; Frijlink, Henderik W.; de Boer, H. Anne

2013-01-01

This paper deals with the effects of mixing time on the homogeneity and dispersion performance of adhesive mixtures for inhalation. Interactions between these effects and the carrier size fraction, the type of drug and the inhalation flow rate were studied. Furthermore, it was examined whether or not changes in the dispersion performance as a result of prolonged mixing can be explained with a balance of three processes that occur during mixing, knowing drug redistribution over the lactose carrier; (de-) agglomeration of the drug (and fine lactose) particles; and compression of the drug particles onto the carrier surface. For this purpose, mixtures containing salmeterol xinafoate or fluticasone propionate were mixed for different periods of time with a fine or coarse crystalline lactose carrier in a Turbula mixer. Drug detachment experiments were performed using a classifier based inhaler at different flow rates. Scanning electron microscopy and laser diffraction techniques were used to measure drug distribution and agglomeration, whereas changes in the apparent solubility were measured as a means to monitor the degree of mechanical stress imparted on the drug particles. No clear trend between mixing time and content uniformity was observed. Quantitative and qualitative interactions between the effect of mixing time on drug detachment and the type of drug, the carrier size fraction and the flow rate were measured, which could be explained with the three processes mentioned. Generally, prolonged mixing caused drug detachment to decrease, with the strongest decline occurring in the first 120 minutes of mixing. For the most cohesive drug (salmeterol) and the coarse carrier, agglomerate formation seemed to dominate the overall effect of mixing time at a low inhalation flow rate, causing drug detachment to increase with prolonged mixing. The optimal mixing time will thus depend on the formulation purpose and the choice for other, interacting variables. PMID:23844256

Orally inhaled drug performance testing for product development, registration, and quality control.

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Lastow, Orest; Svensson, Mårten

2014-12-01

A DPI can be split into three different modules; device, formulation, process. These are developed in parallel, and together with the user they provide the performance of an inhalation product. During product development, these modules are evolving and changing, whereas the requirements on an inhalation product are always expressed in terms of the performance of the final commercial product. To do performance testing during development when the product is not finished presents many challenges and can be confusing and misleading. During development, the performance of the final product is typically being predicted by testing ever changing prototypes. This article describes methods and approaches to manage such development and to, during development, provide relevant predictions of the in vitro and in vivo performances of the final product.

Hydrazine inhalation hepatotoxicity.

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Kao, Yung Hsiang; Chong, C H; Ng, W T; Lim, D

2007-10-01

Abstract Hydrazine is a hazardous chemical commonly used as a reactant in rocket and jet fuel cells. Animal studies have demonstrated hepatic changes after hydrazine inhalation. Human case reports of hydrazine inhalation hepatotoxicity are rare. We report a case of mild hepatotoxicity following brief hydrazine vapour inhalation in a healthy young man, which resolved completely on expectant management.

Investigation of electrostatic behavior of a lactose carrier for dry powder inhalers.

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Chow, Keat Theng; Zhu, Kewu; Tan, Reginald B H; Heng, Paul W S

2008-12-01

This study aims to elucidate the electrostatic behavior of a model lactose carrier used in dry powder inhaler formulations by examining the effects of ambient relative humidity (RH), aerosolization air flow rate, repeated inhaler use, gelatin capsule and tapping on the specific charge (nC/g) of bulk and aerosolized lactose. Static and dynamic electrostatic charge measurements were performed using a Faraday cage connected to an electrometer. Experiments were conducted inside a walk-in environmental chamber at 25 degrees C and RHs of 20% to 80%. Aerosolization was achieved using air flow rates of 30, 45, 60 and 75 L/min. The initial charges of the bulk and capsulated lactose were a magnitude lower than the charges of tapped or aerosolized lactose. Dynamic charge increased linearly with aerosolization air flow rate and RH. Greater frictional forces at higher air flow rate induced higher electrostatic charges. Increased RH enhanced charge generation. Repeated inhaler use significantly influenced electrostatic charge due to repeated usage. This study demonstrated the significance of interacting influences by variables commonly encountered in the use DPI such as variation in patient's inspiratory flow rate, ambient RH and repeated inhaler use on the electrostatic behavior of a lactose DPI carrier.

Airborne concentrations of benzene associated with the historical use of some formulations of liquid wrench.

Science.gov (United States)

Williams, Pamela R D; Knutsen, Jeffrey S; Atkinson, Chris; Madl, Amy K; Paustenbach, Dennis J

2007-08-01

The current study characterizes potential inhalation exposures to benzene associated with the historical use of some formulations of Liquid Wrench under specific test conditions. This product is a multiuse penetrant and lubricant commonly used in a variety of consumer and industrial settings. The study entailed the remanufacturing of several product formulations to have similar physical and chemical properties to most nonaerosol Liquid Wrench formulations between 1960 and 1978. The airborne concentrations of benzene and other constituents during the simulated application of these products were measured under a range of conditions. Nearly 200 breathing zone and area bystander air samples were collected during 11 different product use scenarios. Depending on the tests performed, average airborne concentrations of benzene ranged from approximately 0.2-9.9 mg/m(3) (0.08-3.8 ppm) for the 15-min personal samples; 0.1-8 mg/m(3) (0.04-3 ppm) for the 1-hr personal samples; and 0.1-5.1 mg/m(3) (0.04-2 ppm) for the 1-hr area samples. The 1-hr personal samples encompassed two 15-min product applications and two 15-min periods of standing within 5 to 10 feet of the work area. The measured airborne concentrations of benzene varied significantly based on the benzene content of the formulation tested (1%, 3%, 14%, or 30% v/v benzene) and the indoor air exchange rate but did not vary much with the base formulation of the product or the two quantities of Liquid Wrench used. The airborne concentrations of five other volatile chemicals (ethylbenzene, toluene, total xylenes, cyclohexane, and hexane) were also measured, and the results were consistent with the volatility and concentrations of these chemicals in the product tested. A linear regression analysis of air concentration compared with the chemical mole fraction in the solution and air exchange rate provided a relatively good fit to the data. The results of this study should be useful for evaluating potential inhalation

Formulating natural based cosmetic product - irradiated herbal lip balm

International Nuclear Information System (INIS)

Seri Chempaka Mohd Yusof; Ros Anita Ahmad Ramli; Foziah Ali; Zainab Harun

2007-01-01

Herbal lip balm was formulated in efforts to produce a safe product, attractive with multifunctional usage i.e. prevent chap lips, reduce mouth odour and benefits in improving the health quality. Problems faced in constructing formulations of herbal lip balm were focused to the extraction of anthocyanins, the stability of the pigments in the formulations and changes of colour during irradiation for the sterilization of herbal lip balm. Natural pigment, anthocyanin was used as a colorant agent in herbal lip balm, obtained from various herbs and vegetables i.e. Hibiscus sabdariffa L. (roselle), Brassica oleracea var. capitata f. rubra (red cabbage) and Daucus carota (carrot). Water based extraction method was used in extracting the anthocyanins. The incorporation of honey in the formulations improved the colour of the lip balm. The usage of plant based ingredient i.e. cocoa butter substituting the normal based ingredient i.e. petroleum jelly in lip balm also affecting the colour of herbal lip balm. Irradiation at 2.5, 5.0 and 10 kGy was carried out as preservation and reducing of microbial load of the herbal lip balm and changes in colour were observed in formulations irradiated at 10 kGy. (Author)

Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery.

Science.gov (United States)

Bi, Ru; Shao, Wei; Wang, Qun; Zhang, Na

2009-02-01

Growing attentions have been paid to the pulmonary route for systemic delivery of peptide and protein drugs, such as insulin. Advantages of this non-injective route include rapid drug deposition in the target organ, fewer systemic side effects and avoiding first pass metabolism. However, sustained release formulations for pulmonary delivery have not been fully exploited till now. In our study, a novel dry powder inhalation (DPI) system of insulin loaded solid lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release, improved stability and effective inhalation. Firstly, the drug was incorporated into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/- 3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in this procedure. The properties of DPI particles were characterized for their pulmonary delivery potency. Thirdly, the in vivo study of intratracheal instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect and a relative pharmacological bioavailability of 44.40% could be achieved in the group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing potential as an efficient and non-toxic lipophilic colloidal drug carrier for enhanced pulmonary delivery of insulin.

Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modelling.

Science.gov (United States)

Vulović, Aleksandra; Šušteršič, Tijana; Cvijić, Sandra; Ibrić, Svetlana; Filipović, Nenad

2018-02-15

One of the critical components of the respiratory drug delivery is the manner in which the inhaled aerosol is deposited in respiratory tract compartments. Depending on formulation properties, device characteristics and breathing pattern, only a certain fraction of the dose will reach the target site in the lungs, while the rest of the drug will deposit in the inhalation device or in the mouth-throat region. The aim of this study was to link the Computational fluid dynamics (CFD) with physiologically-based pharmacokinetic (PBPK) modelling in order to predict aerolisolization of different dry powder formulations, and estimate concomitant in vivo deposition and absorption of amiloride hydrochloride. Drug physicochemical properties were experimentally determined and used as inputs for the CFD simulations of particle flow in the generated 3D geometric model of Aerolizer® dry powder inhaler (DPI). CFD simulations were used to simulate air flow through Aerolizer® inhaler and Discrete Phase Method (DPM) was used to simulate aerosol particles deposition within the fluid domain. The simulated values for the percent emitted dose were comparable to the values obtained using Andersen cascade impactor (ACI). However, CFD predictions indicated that aerosolized DPI have smaller particle size and narrower size distribution than assumed based on ACI measurements. Comparison with the literature in vivo data revealed that the constructed drug-specific PBPK model was able to capture amiloride absorption pattern following oral and inhalation administration. The PBPK simulation results, based on the CFD generated particle distribution data as input, illustrated the influence of formulation properties on the expected drug plasma concentration profiles. The model also predicted the influence of potential changes in physiological parameters on the extent of inhaled amiloride absorption. Overall, this study demonstrated the potential of the combined CFD-PBPK approach to model inhaled drug

Lipid Based Formulations of Biopharmaceutics Classification System (BCS Class II Drugs: Strategy, Formulations, Methods and Saturation

Directory of Open Access Journals (Sweden)

Šoltýsová I.

2016-12-01

Full Text Available Active ingredients in pharmaceuticals differ by their physico-chemical properties and their bioavailability therefore varies. The most frequently used and most convenient way of administration of medicines is oral, however many drugs are little soluble in water. Thus they are not sufficiently effective and suitable for such administration. For this reason a system of lipid based formulations (LBF was developed. Series of formulations were prepared and tested in water and biorelevant media. On the basis of selection criteria, there were selected formulations with the best emulsification potential, good dispersion in the environment and physical stability. Samples of structurally different drugs included in the Class II of the Biopharmaceutics classification system (BCS were obtained, namely Griseofulvin, Glibenclamide, Carbamazepine, Haloperidol, Itraconazol, Triclosan, Praziquantel and Rifaximin, for testing of maximal saturation in formulations prepared from commercially available excipients. Methods were developed for preparation of formulations, observation of emulsification and its description, determination of maximum solubility of drug samples in the respective formulation and subsequent analysis. Saturation of formulations with drugs showed that formulations 80 % XA and 20 % Xh, 35 % XF and 65 % Xh were best able to dissolve the drugs which supports the hypothesis that it is desirable to identify limited series of formulations which could be generally applied for this purpose.

Clinical studies with oral lipid based formulations of poorly soluble compounds

DEFF Research Database (Denmark)

Fatouros, Dimitrios; Karpf, Ditte M; Nielsen, Flemming S

2007-01-01

. Several drug products intended for oral administration have been marketed utilizing lipid and surfactant based formulations. Sandimmune((R)) and Sandimmune Neoral((R)) (cyclosporin A, Novartis), Norvir((R)) (ritonavir), and Fortovase((R)) (saquinavir) have been formulated in self-emulsifying drug delivery...... systems (SEDDS). This review summarizes published pharmacokinetic studies of orally administered lipid based formulations of poorly aqueous soluble drugs in human subjects. Special attention has been paid to the physicochemical characteristics of the formulations, when available and the impact...

Inhaler technique maintenance: gaining an understanding from the patient's perspective.

Science.gov (United States)

Ovchinikova, Ludmila; Smith, Lorraine; Bosnic-Anticevich, Sinthia

2011-08-01

The aim of this study was to determine the patient-, education-, and device-related factors that predict inhaler technique maintenance. Thirty-one community pharmacists were trained to deliver inhaler technique education to people with asthma. Pharmacists evaluated (based on published checklists), and where appropriate, delivered inhaler technique education to patients (participants) in the community pharmacy at baseline (Visit 1) and 1 month later (Visit 2). Data were collected on participant demographics, asthma history, current asthma control, history of inhaler technique education, and a range of psychosocial aspects of disease management (including adherence to medication, motivation for correct technique, beliefs regarding the importance of maintaining correct technique, and necessity and concern beliefs regarding preventer therapy). Stepwise backward logistic regression was used to identify the predictors of inhaler technique maintenance at 1 month. In total 145 and 127 participants completed Visits 1 and 2, respectively. At baseline, 17% of patients (n = 24) demonstrated correct technique (score 11/11) which increased to 100% (n = 139) after remedial education by pharmacists. At follow-up, 61% (n = 77) of patients demonstrated correct technique. The predictors of inhaler technique maintenance based on the logistic regression model (X(2) (3, N = 125) = 16.22, p = .001) were use of a dry powder inhaler over a pressurized metered-dose inhaler (OR 2.6), having better asthma control at baseline (OR 2.3), and being more motivated to practice correct inhaler technique (OR 1.2). Contrary to what is typically recommended in previous research, correct inhaler technique maintenance may involve more than repetition of instructions. This study found that past technique education factors had no bearing on technique maintenance, whereas patient psychosocial factors (motivation) did.

DEM analysis of the effect of particle-wall impact on the dispersion performance in carrier-based dry powder inhalers.

Science.gov (United States)

Yang, Jiecheng; Wu, Chuan-Yu; Adams, Michael

2015-06-20

The impact between particles or agglomerates and a device wall is considered as an important mechanism controlling the dispersion of active pharmaceutical ingredient (API) particles in dry powder inhalers (DPIs). In order to characterise the influencing factors and better understand the impact induced dispersion process for carrier-based DPIs, the impact behaviour between an agglomerate and a wall is systematically investigated using the discrete element method. In this study, a carrier-based agglomerate is initially formed and then allowed to impact with a target wall. The effects of impact velocity, impact angle and work of adhesion on the dispersion performance are analysed. It is shown that API particles in the near-wall regions are more likely to be dispersed due to the deceleration of the carrier particle resulted from the impact with the wall. It is also revealed that the dispersion ratio increases with increasing impact velocity and impact angle, indicating that the normal component of the impact velocity plays a dominant role on the dispersion. Furthermore, the impact induced dispersion performance for carrier-based DPI formulations can be well approximated using a cumulative Weibull distribution function that is governed by the ratio of overall impact energy and adhesion energy. Copyright © 2015 Elsevier B.V. All rights reserved.

PREPARATION OF ISONIAZID AS DRY POWDER FORMULATIONS FOR INHALATION BY PHYSICAL MIXING AND SPRAY DRYING

Directory of Open Access Journals (Sweden)

SOMCHAI SAWATDEE

2006-01-01

Full Text Available The main purpose of this study is to develop isoniazid as dry powder aerosol for delivery to the lower airways and to study the susceptibility of M. bovis and M. tuberculosis to the formulationsstudied. Isoniazid was formulated with trehalose, mannose and lactose by physical mixing and spray drying techniques. All formulations were evaluated for delivery efficiency and stability.Susceptibility tests of Mycobacterium species to the drug formulations were carried out. Isoniazid mixed with fine trehalose, micronised mannose or fine lactose produced the formulations whichgave fine particle fraction ( 0.05.

Bio-Based Polyols from Seed Oils for Water-Blown Rigid Polyurethane Foam Preparation

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Paweena Ekkaphan

2016-01-01

Full Text Available The preparation of water-blown rigid polyurethane (RPUR foams using bio-based polyols from sesame seed oil and pumpkin seed oil has been reported. Polyols synthesis involved two steps, namely, hydroxylation and alcoholysis reaction. FTIR, NMR, and ESI-MS were used to monitor the process of the synthesized polyols and their physicochemical properties were determined. The resulting polyols have OH number in the range of 340–351 mg KOH/g. RPUR foams blown with water were produced from the reaction of biopolyols with commercial polymeric methylene diphenyl diisocyanate (PMDI. The proper PUR formulations can be manipulated to produce the desired material applications. These seed oil-based RPUR foams exhibited relatively high compressive strength (237.7–240.2 kPa with the density in the range of 40–45 kg/m3. Additionally, the cell foam morphology investigated by scanning electron microscope indicated that their cellular structure presented mostly polygonal closed cells. The experimental results demonstrate that these bio-based polyols can be used as an alternative starting material for RPUR production.

Novel microemulsion-based gel formulation of tazarotene for therapy of acne.

Science.gov (United States)

Patel, Mrunali Rashmin; Patel, Rashmin Bharatbhai; Parikh, Jolly R; Patel, Bharat G

2016-12-01

The objective of this study was to develop and evaluate a novel microemulsion based gel formulation containing tazarotene for targeted topical therapy of acne. Psudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, and co-surfactant for microemulsion formation. The optimized microemulsion formulation containing 0.05% tazarotene was formulated by spontaneous microemulsification method consisting of 10% Labrafac CC, mixed emulsifiers 15% Labrasol-Cremophor-RH 40 (1:1), 15% Capmul MCM, and 60% distilled water (w/w) as an external phase. All plain and tazarotene-loaded microemulsions were clear and showed physicochemical parameters for desired topical delivery and stability. The permeation profiles of tazarotene through rat skin from optimized microemulsion formulation followed the Higuchi model for controlled permeation. Microemulsion-based gel was prepared by incorporating Carbopol®971P NF in optimized microemulsion formulation having suitable skin permeation rate and skin uptake. Microemulsion-based gel showed desired physicochemical parameters and demonstrated advantage over marketed formulation in improving the skin tolerability of tazarotene indicating its potential in improving its topical delivery. The developed microemulsion-based gel may be a potential drug delivery vehicle for targeted topical delivery of tazarotene in the treatment of acne.

New Mechanisms to Explain the Effects of Added Lactose Fines on the Dispersion Performance of Adhesive Mixtures for Inhalation

Science.gov (United States)

Grasmeijer, Floris; Lexmond, Anne J.; van den Noort, Maarten; Hagedoorn, Paul; Hickey, Anthony J.; Frijlink, Henderik W.; de Boer, Anne H.

2014-01-01

Fine excipient particles or ‘fines’ have been shown to improve the dispersion performance of carrier-based formulations for dry powder inhalation. Mechanistic formulation studies have focussed mainly on explaining this positive effect. Previous studies have shown that higher drug contents may cause a decrease in dispersion performance, and there is no reason why this should not be true for fines with a similar shape, size and cohesiveness as drug particles. Therefore, the effects on drug detachment of ‘fine lactose fines’ (FLF, X50 = 1.95 µm) with a similar size and shape as micronised budesonide were studied and compared to those of ‘coarse lactose fines’ (CLF, X50 = 3.94 µm). Furthermore, interactions with the inhalation flow rate, the drug content and the mixing order were taken into account. The observed effects of FLF are comparable to drug content effects in that the detached drug fraction was decreased at low drug content and low flow rates but increased at higher flow rates. At high drug content the effects of added FLF were negligible. In contrast, CLF resulted in higher detached drug fractions at all flow rates and drug contents. The results from this study suggest that the effects of fines may be explained by two new mechanisms in addition to those previously proposed. Firstly, fines below a certain size may increase the effectiveness of press-on forces or cause the formation of strongly coherent fine particle networks on the carrier surface containing the drug particles. Secondly, when coarse enough, fines may prevent the formation of, or disrupt such fine particle networks, possibly through a lowering of their tensile strength. It is recommended that future mechanistic studies are based on the recognition that added fines may have any effect on dispersion performance, which is determined by the formulation and dispersion conditions. PMID:24489969

Personal exposure to inhalable cement dust among construction workers

International Nuclear Information System (INIS)

Peters, Susan; Kromhout, Hans; Thomassen, Yngvar; Fechter-Rink, Edeltraud

2009-01-01

A case study was carried out in 2006-2007 to assess the actual cement dust exposure among construction workers involved in a full-scale construction project and as a comparison among workers involved in various stages of cement and concrete production. Full-shift personal exposure measurements were performed for several job types. Inhalable dust and cement dust (based on analysis of elemental calcium) concentrations were determined. Inhalable dust exposures at the construction site ranged from 0.05 to 34 mg/m3, with a mean concentration of 1.0 mg/m3. For inhalable cement dust mean exposure was 0.3 mg/m3 (range 0.02-17 mg/m3). Reinforcement and pouring workers had the lowest average concentrations. Inhalable dust levels in the ready-mix and pre-cast concrete plants were, on average, below 0.5 mg/m3 for inhalable dust and below 0.2 mg/m3 for inhalable cement dust. Highest dust concentrations were measured in cement production, particularly during cleaning tasks (inhalable dust GM=55 mg/m3; inhalable cement dust GM=33 mg/m3) at which point the workers wore personal protective equipment. Elemental measurements showed highest but very variable cement percentages in the cement plant and very low percentages of cement during reinforcement work and pouring.

Ciclesonide Oral Inhalation

Science.gov (United States)

... use ciclesonide inhalation.Ciclesonide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use ciclesonide ...

Flunisolide Oral Inhalation

Science.gov (United States)

... use flunisolide inhalation.Flunisolide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use flunisolide ...

Ciclesonide: a safe and effective inhaled corticosteroid for the treatment of asthma

Directory of Open Access Journals (Sweden)

Timothy J Schaffner

2009-02-01

Full Text Available Timothy J Schaffner1,2David P Skoner1,2,31Division of Allergy, Asthma, and Immunology, Allegheny General Hospital, Pittsburgh, PA, USA; 2West Virginia University School of Medicine, Morgantown, WV, USA; 3Drexel College of Medicine, Philadelphia, PA, USAAbstract: Ciclesonide is a novel inhaled corticosteroid used in the continuous treatment of mild-to-severe asthma. Its formulation and mechanism of action yield a low oral and systemic bioavailability, and high pulmonary deposition. In multiple clinical trials, ciclesonide is at least as effective as either fluticasone propionate or budesonide at symptom control, while in many cases having improved safety outcomes and tolerability. The improved safety and comparable efficacy profiles of ciclesonide demonstrated in current studies could potentially yield a treatment option that may lead to improved adherence and outcome.Keywords: ciclesonide, asthma, inhaled corticosteroid

Siting criteria based on the prevention of deterministic effects from plutonium inhalation exposures

International Nuclear Information System (INIS)

Sorensen, S.A.; Low, J.O.

1998-01-01

Siting criteria are established by regulatory authorities to evaluate potential accident scenarios associated with proposed nuclear facilities. The 0.25 Sv (25 rem) siting criteria adopted in the United States has been historically based on the prevention of deterministic effects from acute, whole-body exposures. The Department of Energy has extended the applicability of this criterion to radionuclides that deliver chronic, organ-specific irradiation through the specification of a 0.25 Sv (25 rem) committed effective dose equivalent siting criterion. A methodology is developed to determine siting criteria based on the prevention of deterministic effects from inhalation intakes of radionuclides which deliver chronic, organ-specific irradiation. Revised siting criteria, expressed in terms of committed effective dose equivalent, are proposed for nuclear facilities that handle primarily plutonium compounds. The analysis determined that a siting criterion of 1.2 Sv (120 rem) committed effective dose equivalent for inhalation exposures to weapons-grade plutonium meets the historical goal of preventing deterministic effects during a facility accident scenario. The criterion also meets the Nuclear Regulatory Commission and Department of Energy Nuclear Safety Goals provided that the frequency of the accident is sufficiently low

Flow Formulation-based Model for the Curriculum-based Course Timetabling Problem

DEFF Research Database (Denmark)

Bagger, Niels-Christian Fink; Kristiansen, Simon; Sørensen, Matias

2015-01-01

problem. This decreases the number of integer variables signicantly and improves the performance compared to the basic formulation. It also shows competitiveness with other approaches based on mixed integer programming from the literature and improves the currently best known lower bound on one data...... instance in the benchmark data set from the second international timetabling competition.......In this work we will present a new mixed integer programming formulation for the curriculum-based course timetabling problem. We show that the model contains an underlying network model by dividing the problem into two models and then connecting the two models back into one model using a maximum ow...

Ease-of-use preference for the ELLIPTA® dry powder inhaler over a commonly used single-dose capsule dry powder inhaler by inhalation device-naïve Japanese volunteers aged 40 years or older

Directory of Open Access Journals (Sweden)

Komase Y

2014-12-01

preferred to the ELLIPTA DPI for comfort of the mouthpiece by 64% of subjects (OR 3.16, CI 1.97–5.06; P<0.0001. The incidence of handling errors (first attempt was 11% with ELLIPTA and 68% with BREEZHALER; differences in incidence were generally similar when analyzed by age (< or ≥65 years or sex. Conclusion: These data, obtained in an inhalation device-naïve population, suggest that the ELLIPTA DPI is preferred to an established alternative based on its ease-of-use features and is associated with fewer handling errors. Keywords: chronic obstructive pulmonary disease, dry powder inhaler, ELLIPTA®, BREEZHALER™

Message formulation, organization, and navigation schemes for icon-based communication aids.

Science.gov (United States)

Patel, Rupal

2011-01-01

Individuals with severe speech and motor impairments rely on assistive communication devices to convey their needs and desires in social, educational, and vocational situations. Users with limited motor control or literacy often choose to use icon-based devices that afford increased speed of message formulation at the cost of fully generative language formulation on letter-based devices. A major challenge with large vocabulary icon-based systems is rate of communication. Message formulation, vocabulary organization, and navigation schemes can be used to mitigate the trade-off between vocabulary size and communication rate. This paper summarizes our research efforts to leverage semantic frame theory, situational context, and rapid serial visual presentation to improve message formulation speed and completeness in our iconCHAT and RSVP iconCHAT systems. Usability data and persisting challenges are discussed.

Inhalant allergies in children.

Science.gov (United States)

Mims, James W; Veling, Maria C

2011-06-01

Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

Inhalant Abuse and Dextromethorphan.

Science.gov (United States)

Storck, Michael; Black, Laura; Liddell, Morgan

2016-07-01

Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler.

Science.gov (United States)

Longest, P Worth; Golshahi, Laleh; Behara, Srinivas R B; Tian, Geng; Farkas, Dale R; Hindle, Michael

2015-06-01

Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy. The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region. The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5-2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%. The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy.

Inhalant Dependence and its Medical Consequences

Directory of Open Access Journals (Sweden)

Mehmet Hamid Boztaş

2010-12-01

Full Text Available The term of inhalants is used for matters easily vapors. Inhalants are preferred for rapid, positive reinforcement and mild high effects. Products including inhalants are cheap, accessible, legal substances and are prevalently used in community. The prevalence of inhalant use in secondary schools in Turkey is about 5.1%. Inhalant substance dependence is generally observed within 14-15 age group. Age at first use could be as low as 5 to 6 years of age. Substance dependence is more probable in adults working in substance existing places. Inhalant usage is common in disadvantaged groups, children living in street, people with history of crimes, prison, depression, suicide, antisocial attitudes and conflict of family, history of abuse, violence and any other drug dependence and isolated populations. Inhalants are absorbed from lungs, after performing their quick and short effect metabolized by cytochrom P450 enzyme system except inhalant nitrites group which has a depressing effect like alcohol. In chronic use general atrophy, ventricular dilatation and wide sulcus were shown in cerebrum, cerebellum and pons by monitoring brain. Defects are mostly in periventricular, subcortical regions and in white matter. Demyelinization, hyperintensity, callosal slimming and wearing off in white and gray matter margins was also found. Ravages of brain shown by brain monitorisation are more and serious in inhalant dependence than in other dependences. It is important to decrease use of inhalants. Different approaches should be used for subcultures and groups in prevention. Prohibiting all the matters including inhalant is not practical as there are too many substances including inhalants. Etiquettes showing harmful materials can be used but this approach can also lead the children and adolescents recognize these substances easily.. Despite determintal effects of inhalant dependence, there are not yet sufficient number of studies conducted on prevention and

Inhalation Toxicology Research Institute annual report, October 1, 1983-September 30, 1984

International Nuclear Information System (INIS)

Guilmette, R.A.; Medinsky, M.A.

1984-12-01

The report describes research in the following areas: (1) aerosol generation and characterization; (2) deposition and fate of inhaled materials; (3) dose-response relationships for inhaled radionuclides; (4) dose-response relationships for inhaled chemical toxicants; and (5) biological factors that influence dose-response relationships. Project descriptions have been individually entered into the date base

Evaluation and Selection of Gel Base for the Formulation of ...

African Journals Online (AJOL)

Purpose: To formulate dexpanthenol gels with enhanced in vivo absorption properties via skin. Methods: Carboxyvinyl derivatives (Carbopol 980 and Ultrez 10) and poloxamer (Lutrol F 127) were used as the hydrogel base in the formulations. Changes in rheological properties (apparent viscosity and penetration values) ...

A perspective on the developmental toxicity of inhaled nanoparticles

DEFF Research Database (Denmark)

Hougaard, Karin Sørig; Campagnolo, Luisa; Chavatte-Palmer, Pascale

2015-01-01

This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respirat......This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from...... the respiratory tract to the placenta and fetus, but also that adverse effects may occur secondarily to maternal inflammatory responses. The limited database describes several organ systems in the offspring to be potentially sensitive to maternal inhalation of particles, but large uncertainties exist about...

Inhaled ciclesonide versus inhaled budesonide or inhaled beclomethasone or inhaled fluticasone for chronic asthma in adults: a systematic review

Directory of Open Access Journals (Sweden)

Halpin David MG

2006-06-01

Full Text Available Abstract Background Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma. Methods We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer. Results Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P Conclusion There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low

Formulation and Evaluation of Microspheres Based on Gelatin ...

African Journals Online (AJOL)

Formulation and Evaluation of Microspheres Based on Gelatin-Mucin Admixtures for the Rectal Delivery of Cefuroxime Sodium. K C Ofokansi, M U Adikwu. Abstract. Purpose: Swellable microspheres based on polymers or their admixtures are frequently employed as drug delivery systems to achieve a controlled release ...

Synthesis and Characterization of Starch-based Aqueous Polymer Isocyanate Wood Adhesive

Directory of Open Access Journals (Sweden)

Shu-min Wang

2015-09-01

Full Text Available Modified starch was prepared in this work by acid-thinning and oxidizing corn starch with ammonium persulfate. Also, starch-based aqueous polymer isocyanate (API wood adhesive was prepared. The effect of the added amount of modified starch, styrene butadiene rubber (SBR, polymeric diphenylmethane diisocyanate (P-MDI, and the mass concentration of polyvinyl alcohol (PVOH on the bonding strength of starch-based API adhesives were determined by orthogonal testing. The starch-based API adhesive performance was found to be the best when the addition of modified starch (mass concentration 35% was 45 g, the amount of SBR was 3%, the PVOH mass concentration was 10%, and the amount of P-MDI was 18%. The compression shearing of glulam produced by starch-based API adhesive reached bonding performance indicators of I type adhesive. A scanning electron microscope (SEM was used to analyze the changes in micro-morphology of the starch surface during each stage. Fourier transform infrared spectroscopy (FT-IR was used to study the changes in absorption peaks and functional groups from starch to starch-based API adhesives. The results showed that during starch-based API adhesive synthesis, corn starch surface was differently changed and it gradually reacted with other materials.

Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC and dipalmitoylphosphatidylethanolamine poly(ethylene glycol (DPPE-PEG microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

Directory of Open Access Journals (Sweden)

Meenach SA

2013-01-01

Full Text Available Samantha A Meenach,1,2 Frederick G Vogt,3 Kimberly W Anderson,2,4 J Zach Hilt,2,4 Ronald C McGarry,5Heidi M Mansour1,41Department of Pharmaceutical Sciences-Drug Development Division, University of Kentucky College of Pharmacy, Lexington, KY; 2Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY, USA; 3Analytical Sciences, Product Development, GlaxoSmithKline, King of Prussia, PA; 4Center of Membrane Sciences, University of Kentucky, Lexington, KY, 5Department of Radiation Medicine, University of Kentucky College of Medicine, Lexington, KY, USAAbstract: Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol (PEGylated lipopolymers as microparticulate/nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan® software and were determined to be 600 nm to 1.2 μm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC and powder X-ray diffraction (PXRD were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... KB] Using a metered dose inhaler (inhaler in mouth) Your browser does not support iframes Using a metered dose inhaler (inhaler in mouth) [PDF – 370 KB] Your browser does not support ...

Inhalant drug use and street youth : Ethnographic insights from Mexico City

NARCIS (Netherlands)

Gigengack, Roy; Preedy, Victor

2016-01-01

The inhalation of volatile substances with intentions of intoxication affects the lives of marginalized youths around the globe, but remains poorly understood. Based upon long-term ethnographic enquiry, this chapter describes the inhalant use of Mexico City's young street people from their

Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients

DEFF Research Database (Denmark)

Klodzinska, Sylvia Natalie; Priemel, Petra Alexandra; Rades, Thomas

2016-01-01

Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa infec...... and management of biofilm infections caused by P. aeruginosa and discusses critical issues related to novel antimicrobial drug formulation design approaches.......Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa....... aeruginosa from the respiratory tract after a first infection has been shown to delay chronic pulmonary infection with the bacteria for up to two years. The challenges with providing a suitable treatment for bacterial sinusitis include: (i) identifying a suitable antimicrobial compound; (ii) selecting...

Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA.

Science.gov (United States)

Jensen, Ditte Krohn; Jensen, Linda Boye; Koocheki, Saeid; Bengtson, Lasse; Cun, Dongmei; Nielsen, Hanne Mørck; Foged, Camilla

2012-01-10

Matrix systems based on biocompatible and biodegradable polymers like the United States Food and Drug Administration (FDA)-approved polymer poly(DL-lactide-co-glycolide acid) (PLGA) are promising for the delivery of small interfering RNA (siRNA) due to favorable safety profiles, sustained release properties and improved colloidal stability, as compared to polyplexes. The purpose of this study was to design a dry powder formulation based on cationic lipid-modified PLGA nanoparticles intended for treatment of severe lung diseases by pulmonary delivery of siRNA. The cationic lipid dioleoyltrimethylammoniumpropane (DOTAP) was incorporated into the PLGA matrix to potentiate the gene silencing efficiency. The gene knock-down level in vitro was positively correlated to the weight ratio of DOTAP in the particles, and 73% silencing was achieved in the presence of 10% (v/v) serum at 25% (w/w) DOTAP. Optimal properties were found for nanoparticles modified with 15% (w/w) DOTAP, which reduced the gene expression with 54%. This formulation was spray-dried with mannitol into nanocomposite microparticles of an aerodynamic size appropriate for lung deposition. The spray-drying process did not affect the physicochemical properties of the readily re-dispersible nanoparticles, and most importantly, the in vitro gene silencing activity was preserved during spray-drying. The siRNA content in the powder was similar to the theoretical loading and the siRNA was intact, suggesting that the siRNA is preserved during the spray-drying process. Finally, X-ray powder diffraction analysis demonstrated that mannitol remained in a crystalline state upon spray-drying with PLGA nanoparticles suggesting that the sugar excipient might exert its stabilizing effect by sterical inhibition of the interactions between adjacent nanoparticles. This study demonstrates that spray-drying is an excellent technique for engineering dry powder formulations of siRNA nanoparticles, which might enable the local

'In-vivo' and bioassay results from two contrasting cases of plutonium-239 inhalation

International Nuclear Information System (INIS)

Ramsden, D.; Bains, M.E.D.; Fraser, D.C.

1969-06-01

'In-vivo' and bioassay measurements following two incidents involving plutonium-239 inhalation are described and contrasted. Incident 1, involving the inhalation of insoluble plutonium oxide, resulted in a lung content of about 20 nCi after the initial clearance. Urine excretion was negligible and the estimation of exposure was based on 'in-vivo' data and faecal excretion. Incident,2, involving the inhalation of soluble plutonium, proved negligible and the estimation of exposure, based on urinary excretion, was 0.6 nCi. (author)

Electrostatic Properties of Particles for Inhalation

OpenAIRE

Rowland, Martin

2015-01-01

Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) aredevices used to deliver therapeutic agents to the lungs. Typically, inhaled activepharmaceutical ingredients (APIs) are electrically resistive materials and are prone toaccumulating electrostatic charge. The build-up of charge on inhaled therapeutics hastraditionally been viewed as a nuisance as it may result in problems such as weighingerrors, agglomeration, adhesion to surfaces and poor flow. Energetic processing st...

Inhalation of uranium ores

International Nuclear Information System (INIS)

Stuart, B.O.; Jackson, P.O.

1975-01-01

In previous studies the biological dispositions of individual long-lived alpha members of the uranium chain ( 238 U, 234 U and 230 Th) were determined during and following repeated inhalation exposures of rats to pitchblende (26 percent U 3 O 8 ) ore. Although finely dispersed ore in secular equilibrium was inhaled, 230 Th/ 234 U radioactivity ratios in the lungs rose from 1.0 to 2.5 during 8 weeks of exposures and increased to 9.2 by four months after cessation of exposures. Marked non-equilibrium levels were also found in the tracheobronchial lymph nodes, kidneys, liver, and femur. Daily exposures of beagle dogs to high levels of this ore for 8 days resulted in lung 230 Th/ 234 U ratios of >2.0. Daily exposures of dogs to lower levels (0.1 mg/1) for 6 months, with sacrifice 15 months later, resulted in lung and thoracic lymph node 230 Th/ 234 U ratios ranging from 3.6 to 9 and nearly 7, respectively. The lungs of hamsters exposed to carnotite (4 percent U 3 O 8 ) ore in current lifespan studies show 230 Th/ 234 U ratios as high as 2.0 during daily inhalation of this ore in secular equilibrium. Beagle dogs sacrificed after several years of daily inhalations of the same carnotite ore plus radon daughters also showed marked non-equilibrium ratios of 230 Th/ 234 U, ranging from 5.6 to 7.4 in lungs and 6.2 to 9.1 in thoracic lymph nodes. This pattern of higher retention of 230 Th than 234 U in lungs, thoracic lymph nodes, and other tissues is thus consistent for two types of uranium ore among several species and suggests a reevaluation of maximum permissible air concentrations of ore, currently based only on uranium content

Inhaled americium dioxide

International Nuclear Information System (INIS)

Park, J.F.

1982-01-01

This project includes experiments to determine the effects of Zn-DTPA therapy on the retention, translocation and biological effects of inhaled 241 AmO 2 . Beagle dogs that received inhalation exposure to 241 AmO 2 developed leukopenia, clincial chemistry changes associated with hepatocellular damage, and were euthanized due to respiratory insufficiency caused by radiation pneumonitis 120 to 131 days after pulmonary deposition of 22 to 65 μCi 241 Am. Another group of dogs that received inhalation exposure to 241 AmO 2 and were treated daily with Zn-DTPA had initial pulmonary deposition of 19 to 26 μCi 241 Am. These dogs did not develop respiratory insufficiency, and hematologic and clinical chemistry changes were less severe than in the non-DTPA-treated dogs

Intumescent formulations based on lignin and phosphinates for the bio-based textiles

Science.gov (United States)

Mandlekar, N.; Cayla, A.; Rault, F.; Giraud, S.; Salaün, F.; Malucelli, G.; Guan, J.

2017-10-01

This study investigates new intumescent formulations based on lignin and phosphinates to improve the flame retardant properties of Polyamide 11, while preserving the bio-based characteristics of this latter. Lignin has the advantage of being a bio-based compound and can be effectively used as carbon source for the design of intumescent systems in combination with other flame retardant additives. Metal phosphinates belong to a novel class of phosphorus flame retardants. Despite their increasing use, there is lack of scientific understanding as far as their fire retardancy mechanism is considered, especially in char forming polymeric materials. In this context, Polyamide 11 was melt blended with lignin and metal phosphinates. The possibility of melt spinning the prepared blends were assessed through melt flow index (MFI) tests; thermogravimetric (TG) analyses and cone calorimetry tests were exploited for investigating the thermal stability and the combustion behaviour of the obtained products, respectively. MFI results indicate that some formulations are suitable for melt spinning processes to generate flame retardant multifilament. Furthermore, the combination of lignin and phosphinates provides charring properties to polyamide 11. Finally, cone calorimetry data confirmed that the designed intumescent formulations could remarkably reduce PHRR through formation of protective char layer, hence slowing down the combustion process.

Factors related to the incorrect use of inhalers by asthma patients

Directory of Open Access Journals (Sweden)

Paulo de Tarso Roth Dalcin

2014-01-01

Full Text Available OBJECTIVE: To evaluate inhaler technique in outpatients with asthma and to determine associations between the correctness of that technique and the level of asthma control. METHODS: This was a cross-sectional study involving patients > 14 years of age with physician-diagnosed asthma. The patients were recruited from the Asthma Outpatient Clinic of the Hospital de Clínicas de Porto Alegre, in the city of Porto Alegre, Brazil. The patients completed two questionnaires (a general questionnaire and an asthma control questionnaire based on the 2011 Global Initiative for Asthma guidelines, demonstrated their inhaler technique, and performed pulmonary function tests. Incorrect inhaler technique was defined as the incorrect execution of at least two of the predefined steps. RESULTS: We included 268 patients. Of those, 81 (30.2% showed incorrect inhaler technique, which was associated with poor asthma control (p = 0.002. Logistic regression analysis identified the following factors associated with incorrect inhaler technique: being widowed (OR = 5.01; 95% CI, 1.74-14.41; p = 0.003; using metered dose inhalers (OR = 1.58; 95% CI, 1.35-1.85; p 2 comorbidities (OR = 3.80; 95% CI, 1.03-14.02; p = 0.045. CONCLUSIONS: In the sample studied, incorrect inhaler technique was associated with poor asthma control. Widowhood, use of metered dose inhalers, low socioeconomic level, and the presence of > 2 comorbidities were associated with incorrect inhaler technique.

Inhalants

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Inhalation Toxicology Research Institute annual report 1987-1988

International Nuclear Information System (INIS)

Mauderly, J.L.; Mewhinney, J.A.; Bechtold, W.E.; Sun, J.D.; Coons, T.A.

1988-12-01

section, Deposition and Fate of Inhaled Toxicants, describes factors influencing the uptake of inhaled materials and their initial interactions in the body. The third and fourth sections, Health Effects of Inhaled Radionuclides and Health Effects of Inhaled Chemical Toxicants, describe recent progress in the fields of radiation and chemical toxicology, respectively. The fifth section, Mechanisms of Carcinogenesis, reflects progress in the understanding of the mechanisms by which radiation and chemicals induce cancer. Similarly, the sixth section, Mechanisms of Non-Carcinogenic Responses to Inhaled Toxicants describes research on the development of diseases other than cancer. The seventh section, The Application of Mathematical Modeling to Health Issues, describes efforts to predict health risks by using computer-based models and limited experimental or epidemiological data. The final section, Studies at the University of Utah, describes progress in studies conducted by University of Utah scientists funded by subcontract through this Institute

Inhalation Toxicology Research Institute annual report 1987-1988

Energy Technology Data Exchange (ETDEWEB)

Mauderly, J L; Mewhinney, J A; Bechtold, W E; Sun, J D; Coons, T A [eds.

1988-12-01

section, Deposition and Fate of Inhaled Toxicants, describes factors influencing the uptake of inhaled materials and their initial interactions in the body. The third and fourth sections, Health Effects of Inhaled Radionuclides and Health Effects of Inhaled Chemical Toxicants, describe recent progress in the fields of radiation and chemical toxicology, respectively. The fifth section, Mechanisms of Carcinogenesis, reflects progress in the understanding of the mechanisms by which radiation and chemicals induce cancer. Similarly, the sixth section, Mechanisms of Non-Carcinogenic Responses to Inhaled Toxicants describes research on the development of diseases other than cancer. The seventh section, The Application of Mathematical Modeling to Health Issues, describes efforts to predict health risks by using computer-based models and limited experimental or epidemiological data. The final section, Studies at the University of Utah, describes progress in studies conducted by University of Utah scientists funded by subcontract through this Institute.

Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections.

Science.gov (United States)

Bodier-Montagutelli, Elsa; Morello, Eric; L'Hostis, Guillaume; Guillon, Antoine; Dalloneau, Emilie; Respaud, Renaud; Pallaoro, Nikita; Blois, Hélène; Vecellio, Laurent; Gabard, Jérôme; Heuzé-Vourc'h, Nathalie

2017-08-01

Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context. Recent phage formulation and aerosolization attempts are also reviewed, raising technical challenges to achieve efficient pulmonary deposition via inhalation. Expert opinion: Overall, the inhalation of phages as antibacterial treatment seems both clinically relevant and technically feasible. Several crucial points still need to be investigated, such as phage product pharmacokinetics and immunogenicity. Furthermore, given phage-specific features, appropriate regulatory and manufacturing guidelines will need to be defined. Finally, randomized controlled clinical trials should be carried out to establish phage therapy's clinical positioning in the antimicrobial arsenal against RTIs.

Design of a device for simultaneous particle size and electrostatic charge measurement of inhalation drugs.

Science.gov (United States)

Zhu, Kewu; Ng, Wai Kiong; Shen, Shoucang; Tan, Reginald B H; Heng, Paul W S

2008-11-01

To develop a device for simultaneous measurement of particle aerodynamic diameter and electrostatic charge of inhalation aerosols. An integrated system consisting of an add-on charge measurement device and a liquid impinger was developed to simultaneously determine particle aerodynamic diameter and electrostatic charge. The accuracy in charge measurement and fine particle fraction characterization of the new system was evaluated. The integrated system was then applied to analyze the electrostatic charges of a DPI formulation composed of salbutamol sulphate-Inhalac 230 dispersed using a Rotahaler. The charge measurement accuracy was comparable with the Faraday cage method, and incorporation of the charge measurement module had no effect on the performance of the liquid impinger. Salbutamol sulphate carried negative charges while the net charge of Inhalac 230 and un-dispersed salbutamol sulphate was found to be positive after being aerosolized from the inhaler. The instantaneous current signal was strong with small noise to signal ratio, and good reproducibility of charge to mass ratio was obtained for the DPI system investigated. A system for simultaneously measuring particle aerodynamic diameter and aerosol electrostatic charges has been developed, and the system provides a non-intrusive and reliable electrostatic charge characterization method for inhalation dosage forms.

Influence of chemical treatment on the tensile properties of kenaf fiber reinforced thermoplastic polyurethane composite

Directory of Open Access Journals (Sweden)

Y. A. El-Shekeil

2012-12-01

Full Text Available In this study, the effect of polymeric Methylene Diphenyl Diisocyanate (pMDI chemical treatment on kenaf (Hibiscus cannabinus reinforced thermoplastic polyurethane (TPU/KF was examined using two different procedures. The first consisted of treating the fibers with 4% pMDI, and the second involved 2% NaOH + 4% pMDI. The composites were characterized according to their tensile properties, Fourier Transform Infrared Spectroscopy (FTIR and Scanning Electron Microscopy (SEM. The treatment of the composite with 4% pMDI did not significantly affect its tensile properties, but the treatment with 2% NaOH + 4% pMDI significantly increased the tensile properties of the composite (i.e., 30 and 42% increases in the tensile strength and modulus, respectively. FTIR also showed that treatment with 2% NaOH + 4% pMDI led to the strongest H-bonding. Additionally, the surface morphology of specimens after tensile fracture confirmed that the composite treated with 2% NaOH + 4% pMDI had the best adhesion and wettability.

In-vitro release of diclofenac diethylammonium from lipid-based formulations.

Science.gov (United States)

Parsaee, Siamak; Sarbolouki, Mohammad N; Parnianpour, Mohamad

2002-07-08

This article presents the preparation and topical performance of some new lipid-based formulations of diclofenac, namely (a) a diclofenac aqueous gel containing mixed micelles (sodium cholate:egg lecithin molar ratio 0.55); (b) diclofenac lotion that contains soya lecithin, ethanol and buffer; and (c) diclofenac lipogel containing egg lecithin, isopropyl myristate, propylene glycol and ethanol. Gel formulations were prepared using Carbomer 934. Release of diclofenac from all formulations was monitored via dialysis through Spectra/por membrane into phosphate buffer (0.2 M pH=7.4) using a Franz cell. Drug release profile and diffusion coefficients were compared with brand formulation (Geigy's Vlotaren Emulgel). Statistical analysis of data show that the diffusion coefficient of the drug from these formulations rank according to the following order: Diclofenac lotion (D=5.308x10(-7) cm(2)/s) >lipogel (D=2.102 x 10(-7) cm(2)/s) >Voltaren Emulgel (1.518 x 10(-7) cm(2)/s) >aqueous gel mixed micelle (0.966 x 10(-7) cm(2)/s). These results show that diclofenac lotion and lipogel maybe more suitable formulations than the conventional topical dosage form.

ANTIMICROBIAL PROPERTIES «LIPIN» INHALATION USE IN CHILDREN WITH ASTHMA

Directory of Open Access Journals (Sweden)

Chernusky V.G.

2016-06-01

relapse. From this it follows that even effective sanitation agents in bronchopulmonary system, the traditional routes of administration of antibacterial drugs, properly selected, taking into account the sensitivity of pathogens to them, does not prevent it from subsequent reinfection relevant pathogens located in the throat and in the bronchopulmonary system. One way to solve this problem is to use as the dosage form liposomes, which are limited microvolumes arising by self-assembly of amphiphilic lipid complexes. The basis of selection of such a drug we used in the clinic used liposomal preparation «Lipin» inhalation at dosages of age through an ultrasonic inhaler in addition to basic therapy recommended by GINA (2012 in two stages. The first stage is achieved by using «Lipin» in 135 children with asthma, aged 5 to 14 years in acute inhalation through an ultrasonic nebulizer in age dosage of 5-10 mg / kg, depending on the age of one inhalation 2 times a day for 7-10 days in children with asthma. This is the effect of biocompatibility with enzymatic and immunological systems of the body, it is anti-microbial and anti-inflammatory effect «Lipin» due to their constituent natural phospholipids - phosphatidylcholine. The second stage of antimicrobial therapy for supporting sanitizing effect is based on the ability to «Lipin» in saline to accumulate on the damaged parts of mucous bronchopulmonary tree and provide prolonged antimicrobial effect and thus prevent the proliferation of pathogenic and opportunistic microorganisms. Comparison of the spectrum of antimicrobial activity of liposomal drug «Lipin» in saline to microorganisms isolated from the sputum of an inhalation after treatment showed that antimicrobial activity «Lipin» advantageously provides bactericidal effect against pathogenic and conditionally pathogenic microorganisms. It should be noted that this formulation does not have a significant impact on the indigenous microflora of the mucous bronchial

A Spreadsheet-Based, Matrix Formulation Linear Programming Lesson

DEFF Research Database (Denmark)

Harrod, Steven

2009-01-01

The article focuses on the spreadsheet-based, matrix formulation linear programming lesson. According to the article, it makes a higher level of theoretical mathematics approachable by a wide spectrum of students wherein many may not be decision sciences or quantitative methods majors. Moreover...

Sevoflurane-Based Inhalation Induction in High-Risk Elderly Patients During Noncardiac Surgery

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O. A. Grebenchikov

2011-01-01

Full Text Available Objective: to study the hemodynamic effects of sevoflurane during the induction of anesthesia in elderly patients at high risk for cardiac events. Subjects and methods. This study enrolled 32 patients who had a left ventricular ejection fraction of <30% during preoperative examination. According to the presumptive type of anesthesia, the patients were randomized to one of the study groups: In the sevoflurane group receiving infusion of fentanyl (1 ig^kg”‘^hr”‘, anesthesia was induced by sevoflurane at the maximum concentration of 8 vol% at first inspiration, without the respiratory circuit being prefilled. After loss of consciousness, further saturation was carried out using Fianesth, 5 vol%. Combination anesthesia (CA was that which was induced by successive administration of dormicum, ketamine, propo-fol, and fentanyl. The trachea was intubated during total myoplegia under the control of TOF (TOF-Watch, Organon, the Netherlands. Results. In all the patients under CA, its induction was made during infusion of dopamine (5 lg^kg”‘^min”‘, the dose of which had to be increased up to 10 ig • kg-1 • min-1 in 6 (75% patients. Nevertheless, there were decreases in mean blood pressure (BPmean to 46±6 mm Hg and in cardiac index (CI to 1.5±0.3 fig • kg-1 • min-1 (by 32% of the outcome value. In the sevoflurane inhalation induction group, only 3 (12.5% patients needed dopamine. Its dose producing a cardiotonic effect was near-minimal; its average maintenance infusion rate was 5.3±0.3 ig^kg”‘^min”‘. The reduction in CI was statistically insignificant; despite a 9% decrease in BPmean, this indicator in the sevoflurane group remained within acceptable ranges. Conclusion. The use of a sevoflurane-based inhalation induction technique permits higher hemodynamic stability in patients at high risk for cardiac events. Key words: inhalation induction, sevoflurane, ketamine, elderly patients.

Influence of inhaled Ca-DTPA on the long-term effects of inhaled Pu nitrate

International Nuclear Information System (INIS)

Ballou, J.E.; Dagle, G.E.; McDonald, K.E.; Buschbom, R.L.

1975-01-01

Inhaled Ca-DTPA administered to rats in 6 weekly, one-hour treatments of 3 mg/rat did not affect weight gain or life-span compared to Pu burdened animals (78 nCi ILB) or nontreated controls. In addition, the drug did not appear to promote the development of malignant lung tumors and bone tumors in Pu burdened rats although one rat exposed only to Ca-DTPA aerosols did develop a malignant lung tumor. This single lung tumor can not be considered significant although the normal incidence of this lesion is quite low. Inhaled Ca-DTPA therapy administered 20 days after Pu inhalation showed little effect in reducing the lung burden of plutonium. Skeletal deposition was decreased possibly because Ca-DTPA was administered during a time of active translocation of the inhaled Pu when Pu may have been available for chelation in the blood. Inhaled Ca-DTPA therapy did not appear to be beneficial in reducing the number of malignant lung tumors or bone tumors in plutonium burdened rats but on the other hand the chelate did not appear to promote these lesions. (U.S.)

Evaluation of Two Commercially Available Cannabidiol Formulations for use in Electronic Cigarettes

OpenAIRE

Michelle R Peace; Karen E Butler; Carl E. Wolf; Carl E. Wolf; Justin L Poklis; Alphonse Poklis; Alphonse Poklis; Alphonse Poklis

2016-01-01

With 24 states and the District of Columbia with laws legalizing marijuana in some form, suppliers of legal marijuana have developed Cannabis sativa products for use in electronic cigarettes. Personal battery powered vaporizers or electronic cigarettes were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. The liquid formulations used in these devices are comprised of an active ingredient such as ni...

FORMATE-BASED FLUIDS: FORMULATION AND APPLICATION

Directory of Open Access Journals (Sweden)

Nediljka Gaurina-Međimurec

2008-12-01

Full Text Available Formate-based fluids has been successfully used in over hunders HPHT well operations since they introduced in field practice. They have many advantages when compared with conventional HPHT drilling and completion fluids such as: minimal formation damage, maintenance of additve properties at high temperatures, reduced hydraulic flow resistance, low potential for differential sticking, naturally lubricating, very low corrosion rates, biodegradable and pose little risk to the environment etc. Formate-based fluids can be applied during deep slim hole drilling, shale drilling, reservoir drilling, salt and gas hydrate formations drilling. The laboratory research was carried out to evaluate the rheological behavior of formate-based fluids as a function of temperature. Formate-based fluids were formulated using potassium formate brine, xanthan polymer, PAC, starch and calcium carbonate. Experimental results show that potassium formate improves the thermal stability of polymers.

Inhalation Injury: State of the Science 2016.

Science.gov (United States)

Foster, Kevin N; Holmes, James H

This article summarizes research conducted over the last decade in the field of inhalation injury in thermally injured patients. This includes brief summaries of the findings of the 2006 State of the Science meeting with regard to inhalation injury, and of the subsequent 2007 Inhalation Injury Consensus Conference. The reviewed studies are categorized in to five general areas: diagnosis and grading; mechanical ventilation; systemic and inhalation therapy; mechanistic alterations; and outcomes.

Soft, chewable gelatin-based pharmaceutical oral formulations: a technical approach.

Science.gov (United States)

Dille, Morten J; Hattrem, Magnus N; Draget, Kurt I

2018-06-01

Hard tablets and capsules for oral drug delivery cause problems for people experiencing dysphagia. This work describes the formulation and properties of a gelatin based, self-preserved, and soft chewable tablet as an alternative and novel drug delivery format. Gelatin (8.8-10% in 24.7-29% water) constituted the matrix of the soft, semi-solid tablets. Three different pharmaceuticals (Ibuprofen 10%, Acetaminophen 15%, and Meloxicam 1.5%) were tested in this formulation. Microbial stability was controlled by lowering the water activity with a mixture of sorbitol and xylitol (45.6-55%). Rheological properties were tested applying small strain oscillation measurements. Taste masking of ibuprofen soft-chew tablets was achieved by keeping the ibuprofen insoluble at pH 4.5 and keeping the processing temperature below the crystalline-to-amorphous transition temperature. Soft-chew formulations showed good stability for all three pharmaceuticals (up to 24 months), and the ibuprofen containing formulation exhibited comparable dissolution to a standard oral tablet as well as good microbial stability. The rheological properties of the ibuprofen/gelatin formulation had the fingerprint of a true gelatin gel, albeit higher moduli, and melting temperature. The results suggest that easy-to-swallow and well taste-masked soft chewable tablet formulations with extended shelf life are within reach for several active pharmaceutical ingredients (APIs).

Chemical-Based Formulation Design: Virtual Experimentation

DEFF Research Database (Denmark)

Conte, Elisa; Gani, Rafiqul

This paper presents a software, the virtual Product-Process Design laboratory (virtual PPD-lab) and the virtual experimental scenarios for design/verification of consumer oriented liquid formulated products where the software can be used. For example, the software can be employed for the design......, the additives and/or their mixtures (formulations). Therefore, the experimental resources can focus on a few candidate product formulations to find the best product. The virtual PPD-lab allows various options for experimentations related to design and/or verification of the product. For example, the selection...... design, model adaptation). All of the above helps to perform virtual experiments by blending chemicals together and observing their predicted behaviour. The paper will highlight the application of the virtual PPD-lab in the design and/or verification of different consumer products (paint formulation...

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... inhaler with a spacer Your browser does not support iframes Using a metered dose inhaler with a ...

High Resolution Mass Spectrometry of Polyfluorinated Polyether-Based Formulation

Science.gov (United States)

Dimzon, Ian Ken; Trier, Xenia; Frömel, Tobias; Helmus, Rick; Knepper, Thomas P.; de Voogt, Pim

2016-02-01

High resolution mass spectrometry (HRMS) was successfully applied to elucidate the structure of a polyfluorinated polyether (PFPE)-based formulation. The mass spectrum generated from direct injection into the MS was examined by identifying the different repeating units manually and with the aid of an instrument data processor. Highly accurate mass spectral data enabled the calculation of higher-order mass defects. The different plots of MW and the nth-order mass defects (up to n = 3) could aid in assessing the structure of the different repeating units and estimating their absolute and relative number per molecule. The three major repeating units were -C2H4O-, -C2F4O-, and -CF2O-. Tandem MS was used to identify the end groups that appeared to be phosphates, as well as the possible distribution of the repeating units. Reversed-phase HPLC separated of the polymer molecules on the basis of number of nonpolar repeating units. The elucidated structure resembles the structure in the published manufacturer technical data. This analytical approach to the characterization of a PFPE-based formulation can serve as a guide in analyzing not just other PFPE-based formulations but also other fluorinated and non-fluorinated polymers. The information from MS is essential in studying the physico-chemical properties of PFPEs and can help in assessing the risks they pose to the environment and to human health.

Toxicological perspectives of inhaled therapeutics and nanoparticles.

Science.gov (United States)

Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

Radioactive gas inhalator

International Nuclear Information System (INIS)

LeMon, D.E.

1975-01-01

An ''inhalator'', or more particularly an apparatus for permitting a patient to inhale a radioactive gas in order to provide a diagnostic test of the patient's lung area, is described. The disclosed apparatus provides a simple, trouble-free mechanism for achieving this result; and, furthermore, provides an improved testing method. Moreover, the disclosed apparatus has the capability of gradually introducing the test condition in a manner that makes it easy for the patient to become acclimated to it. (U.S.)

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... metered dose inhaler with a spacer [ PDF – 377 KB] Your browser does not support iframes Cómo usar ... inhalador de dosis fija con espaciador [PDF – 343 KB] Using a metered dose inhaler (inhaler in mouth) ...

Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition.

Science.gov (United States)

Sørli, Jorid B; Huang, Yishi; Da Silva, Emilie; Hansen, Jitka S; Zuo, Yi Y; Frederiksen, Marie; Nørgaard, Asger W; Ebbehøj, Niels E; Larsen, Søren T; Hougaard, Karin S

2018-01-01

Private consumers and professionals may experience acute inhalation toxicity after inhaling aerosolized impregnation products. The distinction between toxic and non-toxic products is difficult to make for producers and product users alike, as there is no clearly described relationship between the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21 impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if the products inhibited surfactant function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e., the in vitro method predicted all the products that were toxic for mice to inhale. The specificity of the in vitro test was 63%, i.e., the in vitro method found three false positives in the 21 tested products. Six of the products had been involved in accidental human inhalation where they caused acute inhalation toxicity. All of these six products inhibited lung surfactant function in vitro and were toxic to mice.

Inhaled plutonium nitrate in dogs

International Nuclear Information System (INIS)

Dagle, G.E.; Cannon, W.C.; Ragan, H.A.; Watson, C.R.; Stevens, D.L.; Cross, F.T.; Dionne, P.J.; Harrington, T.P.

1978-01-01

Beagle dogs given a single inhalation exposure to 239 Pu(NO 3 ) 4 are being observed for life-span dose-effect relationships. Lymphopenia occurred at the two highest dosage levels as early as 1 mo following exposure and was associated with neutropenia and reduction in numbers of circulatory monocytes by 4 mo postexposure. Radiation pneumonitis developed in one dog at the highest dosage level at 14 mo postexposure. More rapid translocation to skeleton and liver occurred following inhalation of 238 Pu(NO 3 ) 4 than after 239 Pu(NO 3 ) 4 inhalation

Dispersibility of lactose fines as compared to API in dry powders for inhalation.

Science.gov (United States)

Thalberg, Kyrre; Åslund, Simon; Skogevall, Marcus; Andersson, Patrik

2016-05-17

This work investigates the dispersion performance of fine lactose particles as function of processing time, and compares it to the API, using Beclomethasone Dipropionate (BDP) as model API. The total load of fine particles is kept constant in the formulations while the proportions of API and lactose fines are varied. Fine particle assessment demonstrates that the lactose fines have higher dispersibility than the API. For standard formulations, processing time has a limited effect on the Fine Particle Fraction (FPF). For formulations containing magnesium stearate (MgSt), FPF of BDP is heavily influenced by processing time, with an initial increase, followed by a decrease at longer mixing times. An equation modeling the observed behavior is presented. Surprisingly, the dispersibility of the lactose fines present in the same formulation remains unaffected by mixing time. Magnesium analysis demonstrates that MgSt is transferred to the fine particles during the mixing process, thus lubrication both BDP and lactose fines, which leads to an increased FPF. Dry particle sizing of the formulations reveals a loss of fine particles at longer mixing times. Incorporation of fine particles into the carrier surfaces is believed to be behind this, and is hence a mechanism of importance as regards the dispersion performance of dry powders for inhalation. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhalation of nanoplatelets - Theoretical deposition simulations.

Science.gov (United States)

Sturm, Robert

2017-12-01

Primary objective of the contribution was the theoretical prediction of nanoplatelet deposition in the human respiratory tract. Modeling was founded on the hypothetical inhalation of graphene nanoplatelets (GNP) measuring 0.01 and 0.1μm in thickness and adopting a projected area diameter of 1-30μm. Particle uptake was assumed to take place with inhalation flow rates of 250, 500, 750, and 1000cm 3 s -1 , respectively. For an appropriate description of pulmonary particle behavior, transport of GNP in a stochastic lung structure and deposition formulae based on analytical and numerical studies were presupposed. The results obtained from the theoretical approach clearly demonstrate that GNP with a thickness of 0.01μm deposit in the respiratory tract by 20-50%, whereas GNP with a thickness of 0.1μm exhibit a deposition of 20-90%. Larger platelets deposit with higher probability than small ones. Increase of inhalation flow rate is accompanied by decreased deposition in the case of thin GNP, whilst thicker GNP are preferably accumulated in the extrathoracic region. Generation-specific deposition ranges from 0.05 to 7% (0.01μm) and from 0.05 to 9%, with maximum values being obtained in airway generation 20. In proximal airway generations (0-10), deposition is increased with inhalation flow rate, whereas in intermediate to distal generations a reverse effect may be observed. Health consequences of GNP deposition in different lung compartments are subjected to an intense debate. Copyright © 2017. Published by Elsevier GmbH.

Characteristics of reversible and nonreversible COPD and asthma and COPD overlap syndrome patients: an analysis of salbutamol Easyhaler data

Directory of Open Access Journals (Sweden)

Müller V

2016-01-01

Full Text Available Veronika Müller,1 Gabriella Gálffy,1 Márta Orosz,1 Zsuzsanna Kováts,1 Balázs Odler,1 Olof Selroos,2 Lilla Tamási1 1Department of Pulmonology, Semmelweis University, Budapest, Hungary; 2Semeco AB, Ängelholm, Sweden Abstract: The choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result. On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics. In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70% in chronic obstructive pulmonary disease [COPD]; <80% in asthma were included (n=121, age: 57.8±17.3 years. Bronchodilator reversibility (American Thoracic Society/European Respiratory Society criteria was tested in patients with COPD (n=63 and asthma and COPD overlap syndrome (ACOS; n=12. Forty-six asthmatics served as controls. Reversibility was tested with 400 µg salbutamol dry powder inhaler (Buventol Easyhaler, Orion Pharma Ltd, Espoo, Finland. Demographic data and patients’ perceptions of Easyhaler compared with β2-agonist pressurized metered dose inhalers (pMDIs were analyzed. American Thoracic Society/European Respiratory Society guideline defined reversibility was found in 21 out of 63 COPD patients and in two out of 12 ACOS patients. Airway obstruction was more severe in COPD patients as compared with controls (mean FEV1 and FEV1% predicted both P<0.0001. Average response to salbutamol was significantly lower in COPD patients compared with asthma controls (P<0.0001. Reversibility was equally often found in smokers as in never-smokers (33% vs 34%. Nonreversible COPD patients had higher mean weight, body mass index, and FEV1/FVC compared with reversible COPD patients. Most patients preferred Easyhaler and defined its use as simpler and more effective than use of a pMDI. Never-smokers and patients with asthma experienced

Teaching inhaler use in chronic obstructive pulmonary disease patients.

Science.gov (United States)

Lareau, Suzanne C; Hodder, Richard

2012-02-01

To review barriers to the successful use of inhalers in patients with chronic obstructive pulmonary disease (COPD), and the role of the nurse practitioner (NP) in facilitating optimum inhaler use. Review of the national and international scientific literature. Pharmacologic treatment of COPD patients comprises mainly inhaled medications. Incorrect use of inhalers is very common in these individuals. Some of the consequences of poor inhaler technique include reduced therapeutic dosing, medication adherence, and disease stability, which can lead to increased morbidity, decreased quality of life, and a high burden on the healthcare system. Knowledgeable evaluation and frequent reassessment of inhaler use coupled with education of patients, caregivers, and healthcare professionals can significantly improve the benefits COPD patients derive from inhaled therapy. Patient education is vital for correct use of inhalers and to ensure the effectiveness of inhaled medications. The NP has a critical role in assessing potential barriers to successful learning by the patient and improving inhaler technique and medication management. The NP can also facilitate success with inhaled medications by providing up-to-date inhaler education for other healthcare team members, who may then act as patient educators. ©2011 The Author(s) Journal compilation ©2011 American Academy of Nurse Practitioners.

Slag-based saltstone formulations

International Nuclear Information System (INIS)

Langton, C.A.

1987-01-01

Approximately 400 x 10 6 liters of low-level alkaline salt solution will be treated at the Savannah River Plant (SRP) Defense Waste Processing Facility (DWPF) prior to disposal in concrete vaults at SRP. Treatment involves removal of CS + and Sr +2 followed by solidification and stabilization of potential contaminants in saltstone, a hydrated ceramic waste form. Chromium, technetium, and nitrate releases from saltstone can be significantly reduced by substituting hydraulic blast furnace slag for portland cement in the formulation designs. Slag-based mixes are also compatible with Class F fly ash used in saltstone as a functional extender to control heat of hydration and reduce permeability. A monolithic waste form is produced by the hydration of the slag and fly ash. Soluble ion release (NO 3 - ) is controlled by the saltstone microstructure. Chromium and technetium are less leachable from slag mixes compared to cement-based waste forms because these species are chemically reduced to a lower valence state by ferrous iron in the slag and precipitated as relatively insoluble phases, such as CR(OH) 3 and TcO 2 . 5 refs., 4 figs., 4 tabs

Improving Dry Powder Inhaler Performance by Surface Roughening of Lactose Carrier Particles.

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Tan, Bernice Mei Jin; Chan, Lai Wah; Heng, Paul Wan Sia

2016-08-01

This study investigated the impact of macro-scale carrier surface roughness on the performance of dry powder inhaler (DPI) formulations. Fluid-bed processing and roller compaction were explored as processing methods to increase the surface roughness (Ra) of lactose carrier particles. DPI formulations containing either (a) different concentrations of fine lactose at a fixed concentration of micronized drug (isoniazid) or (b) various concentrations of drug in the absence of fine lactose were prepared. The fine particle fraction (FPF) and aerodynamic particle size of micronized drug of all formulations were determined using the Next Generation Impactor. Fluid-bed processing resulted in a modest increase in the Ra from 562 to 907 nm while roller compaction led to significant increases in Ra > 1300 nm. The roller compacted carriers exhibited FPF > 35%, which were twice that of the smoothest carriers. The addition of up to 5%, w/w of fine lactose improved the FPF of smoother carriers by 60-200% whereas only lactose carrier particles by roller compaction was immensely beneficial to improving DPI performance, primarily due to increased surface roughness at the macro-scale.

A Lagrange-Eulerian formulation of an axially moving beam based on the absolute nodal coordinate formulation

Energy Technology Data Exchange (ETDEWEB)

Pechstein, Astrid, E-mail: astrid.pechstein@jku.at [Johannes Kepler University Linz, Institute of Technical Mechanics (Austria); Gerstmayr, Johannes, E-mail: johannes.gerstmayr@accm.co.at [Austrian Center of Competence in Mechatronics (Austria)

2013-10-15

In the scope of this paper, a finite-element formulation for an axially moving beam is presented. The beam element is based on the absolute nodal coordinate formulation, where position and slope vectors are used as degrees of freedom instead of rotational parameters. The equations of motion for an axially moving beam are derived from generalized Lagrange equations in a Lagrange-Eulerian sense. This procedure yields equations which can be implemented as a straightforward augmentation to the standard equations of motion for a Bernoulli-Euler beam. Moreover, a contact model for frictional contact between an axially moving strip and rotating rolls is presented. To show the efficiency of the method, simulations of a belt drive are presented.

Use of nitrite inhalants ("poppers") among American youth.

Science.gov (United States)

Wu, Li-Tzy; Schlenger, William E; Ringwalt, Chris L

2005-07-01

We examined the patterns and correlates of nitrite inhalant use among adolescents aged 12 to 17 years. Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Logistic regression was used to identify the characteristics associated with nitrite inhalant use. Among adolescents aged 12 to 17 years, 1.5% reported any lifetime use of nitrite inhalants. The prevalence of lifetime nitrite inhalant use increased to 12% and 14% among adolescents who were dependent on alcohol and any drug in the past year, respectively. Many nitrite inhalant users used at least three other types of inhalants (68%) and also met the criteria for alcohol (33%) and drug (35%) abuse or dependence. Increased odds of nitrite inhalant use were associated with residing in nonmetropolitan areas, recent utilization of mental health services, delinquent behaviors, past year alcohol and drug abuse and dependence, and multi-drug use. Adolescents who had used nitrite inhalants at least once in their lifetime tend to engage in delinquent activities and report co-occurring multiple drug abuse and mental health problems in the past year.

Age dependent systemic exposure to inhaled salbutamol

DEFF Research Database (Denmark)

Bønnelykke, Klaus; Jespersen, Jakob Jessing; Bisgaard, Hans

2007-01-01

AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing...

Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.

Science.gov (United States)

Basheti, Iman A; Obeidat, Nathir M; Reddel, Helen K

2017-02-09

Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0-9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a "Show-and-Tell" inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler -1.04 (95% confidence interval -1.92, -0.16, P = 0.022); Turbuhaler -1.61 (-2.63, -0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes. REMINDER LABELS IMPROVE INHALER TECHNIQUE: Personalized

Method Development for Clinical Comprehensive Evaluation of Pediatric Drugs Based on Multi-Criteria Decision Analysis: Application to Inhaled Corticosteroids for Children with Asthma.

Science.gov (United States)

Yu, Yuncui; Jia, Lulu; Meng, Yao; Hu, Lihua; Liu, Yiwei; Nie, Xiaolu; Zhang, Meng; Zhang, Xuan; Han, Sheng; Peng, Xiaoxia; Wang, Xiaoling

2018-04-01

Establishing a comprehensive clinical evaluation system is critical in enacting national drug policy and promoting rational drug use. In China, the 'Clinical Comprehensive Evaluation System for Pediatric Drugs' (CCES-P) project, which aims to compare drugs based on clinical efficacy and cost effectiveness to help decision makers, was recently proposed; therefore, a systematic and objective method is required to guide the process. An evidence-based multi-criteria decision analysis model that involved an analytic hierarchy process (AHP) was developed, consisting of nine steps: (1) select the drugs to be reviewed; (2) establish the evaluation criterion system; (3) determine the criterion weight based on the AHP; (4) construct the evidence body for each drug under evaluation; (5) select comparative measures and calculate the original utility score; (6) place a common utility scale and calculate the standardized utility score; (7) calculate the comprehensive utility score; (8) rank the drugs; and (9) perform a sensitivity analysis. The model was applied to the evaluation of three different inhaled corticosteroids (ICSs) used for asthma management in children (a total of 16 drugs with different dosage forms and strengths or different manufacturers). By applying the drug analysis model, the 16 ICSs under review were successfully scored and evaluated. Budesonide suspension for inhalation (drug ID number: 7) ranked the highest, with comprehensive utility score of 80.23, followed by fluticasone propionate inhaled aerosol (drug ID number: 16), with a score of 79.59, and budesonide inhalation powder (drug ID number: 6), with a score of 78.98. In the sensitivity analysis, the ranking of the top five and lowest five drugs remains unchanged, suggesting this model is generally robust. An evidence-based drug evaluation model based on AHP was successfully developed. The model incorporates sufficient utility and flexibility for aiding the decision-making process, and can be a useful

Development of high efficiency ventilation bag actuated dry powder inhalers.

Science.gov (United States)

Behara, Srinivas R B; Longest, P Worth; Farkas, Dale R; Hindle, Michael

2014-04-25

New active dry powder inhaler systems were developed and tested to efficiently aerosolize a carrier-free formulation. To assess inhaler performance, a challenging case study of aerosol lung delivery during high-flow nasal cannula (HFNC) therapy was selected. The active delivery system consisted of a ventilation bag for actuating the device, the DPI containing a flow control orifice and 3D rod array, and streamlined nasal cannula with separate inlets for the aerosol and HFNC therapy gas. In vitro experiments were conducted to assess deposition in the device, emitted dose (ED) from the nasal cannula, and powder deaggregation. The best performing systems achieved EDs of 70-80% with fine particle fractions <5 μm of 65-85% and mass median aerodynamic diameters of 1.5 μm, which were target conditions for controlled condensational growth aerosol delivery. Decreasing the size of the flow control orifice from 3.6 to 2.3mm reduced the flow rate through the system with manual bag actuations from an average of 35 to 15LPM, while improving ED and aerosolization performance. The new devices can be applied to improve aerosol delivery during mechanical ventilation, nose-to-lung aerosol administration, and to assist patients that cannot reproducibly use passive DPIs. Copyright © 2014 Elsevier B.V. All rights reserved.

E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices.

Science.gov (United States)

Steinberg, Michael B; Zimmermann, Mia Hanos; Delnevo, Cristine D; Lewis, M Jane; Shukla, Parth; Coups, Elliot J; Foulds, Jonathan

2014-11-01

Novel nicotine delivery products, such as electronic cigarettes (e-cigarettes), have dramatically grown in popularity despite limited data on safety and benefit. In contrast, the similar U.S. Food and Drug Administration (FDA)-approved nicotine inhaler is rarely utilized by smokers. Understanding this paradox could be helpful to determine the potential for e-cigarettes as an alternative to tobacco smoking. To compare the e-cigarette with the nicotine inhaler in terms of perceived benefits, harms, appeal, and role in assisting with smoking cessation. A cross-over trial was conducted from 2012 to 2013 PARTICIPANTS/INTERVENTIONS: Forty-one current smokers age 18 and older used the e-cigarette and nicotine inhaler each for 3 days, in random order, with a washout period in between. Thirty-eight participants provided data on product use, perceptions, and experiences. The Modified Cigarette Evaluation Questionnaire (mCEQ) measured satisfaction, reward, and aversion. Subjects were also asked about each product's helpfulness, similarity to cigarettes, acceptability, image, and effectiveness in quitting smoking. Cigarette use was also recorded during the product-use periods. The e-cigarette had a higher total satisfaction score (13.9 vs. 6.8 [p e-cigarette received higher ratings for helpfulness, acceptability, and "coolness." More subjects would use the e-cigarette to make a quit attempt (76 %) than the inhaler (24 %) (p e-cigarette vs. 10 % (4/38) using the inhaler (p = 0.18). The e-cigarette was more acceptable, provided more satisfaction, and had higher perceived benefit than the inhaler during this trial. E-cigarettes have the potential to be important nicotine delivery products owing to their high acceptance and perceived benefit, but more data are needed to evaluate their actual efficacy and safety. Providers should be aware of these issues, as patients will increasingly inquire about them.

Assessment of Plant-Probiotic Performance of Novel Endophytic Bacillus sp. in Talc-Based Formulation.

Science.gov (United States)

Basheer, Jasim; Ravi, Aswani; Mathew, Jyothis; Krishnankutty, Radhakrishnan Edayileveettil

2018-01-25

Endophytic bacteria are considered to have a plethora of plant growth promoting and anti-phytopathogenic traits to live within the plants. Hence, they have immense promises for plant probiotic development. In the current study, plant probiotic endophytic Bacillus sp. CaB5 which has been previously isolated from Capsicum annuum was investigated for its performance in talc-based formulation. For this, CaB5 was made into formulation with sterile talc, calcium carbonate, and carboxymethyl cellulose. The viability analysis of the formulation by standard plate count and fluorescence methods has confirmed the stable microbial count up to 45 days. Plant probiotic performance of the prepared formulation was analyzed on cowpea (Vigna unguiculata) and lady's finger (Abelmoschus esculentus). The results showed the formulation treatment to have enhancement effect on seed germination as well as plant growth in both selected plants. The results highlight the potential of CaB5-based formulation for field application to enhance growth of economically important plants.

Bacillus subtilis based-formulation for the control of postbloom fruit drop of citrus.

Science.gov (United States)

Klein, Mariana Nadjara; da Silva, Aline Caroline; Kupper, Katia Cristina

2016-12-01

Postbloom fruit drop (PFD) caused by Colletotrichum acutatum affects flowers and causes early fruit drop in all commercial varieties of citrus. Biological control with the isolate ACB-69 of Bacillus subtilis has been considered as a potential method for controlling this disease. This study aimed to develop and optimize a B. subtilis based-formulation with a potential for large-scale applications and evaluate its effect on C. acutatum in vitro and in vivo. Bacillus subtilis based-formulations were developed using different carrier materials, and their ability to control PFD was evaluated. The results of the assays led to the selection of the B. subtilis based-formulation with talc + urea (0.02 %) and talc + ammonium molybdate (1 mM), which inhibited mycelial growth and germination of C. acutatum. Studies with detached citrus flowers showed that the formulations were effective in controlling the pathogen. In field conditions, talc + urea (0.02 %) provided 73 % asymptomatic citrus flowers and 56 % of the average number of effective fruit (ANEF), equating with fungicide treatment. On the contrary, non-treated trees had 8.8 % of asymptomatic citrus flowers and 0.83 % ANEF. The results suggest that B. subtilis based-formulations with talc as the carrier supplemented with a nitrogen source had a high potential for PFD control.

Administration of cyclosporine by inhalation: A feasibility study in Beagle dogs

International Nuclear Information System (INIS)

Muggenburg, B.A.; Hoover, M.D.; Haley, P.J.; Snipes, M.B.; Wolff, R.K.; Yeh, H.C.; Griffith, B.P.; Burckart, J.; Mauderly, J.L.

1988-01-01

Oral cyclosporine inhibits the primary,but-not the secondary immune responses in the lung. These findings suggest that the local administration of cyclosporine by inhalation could be a useful tool for increasing our understanding of lung immunity. Five dogs were each treated with inhaled, oral and intravenous cyclosporine, aerosol vehicle (ethyl alcohol), and no treatment, over a 5-wk period. One treatment per week was given to each dog. A radiolabel, 99m Tc was included in the cyclosporine aerosol to allow visualization of lung distribution of the aerosol. Blood plasma concentrations of cyclosporine were approximately the same at 4 h and were essentially cleared by 24 h for all routes of administration. Aerosol distribution in the lung appeared uniform, based on 99m Tc scintigrams. In a second study, two dogs inhaled cyclosporine once a day for five days, two dogs inhaled the aerosol vehicle, and one dog was not treated. No evidence of acute lung injury, based on cell counts, total protein, alkaline phosphatase, or lactic dehydrogenase levels in the bronchoalveolar lavage fluid, was found at 24 h after one or five administrations of cyclosporine. These data indicate that cyclosporine administered by aerosol either once or five times was distributed throughout the lung and was absorbed into the blood without producing an acute inflammatory reaction in the lung. Our results suggest that cyclosporine may be safely given by inhalation for studies of local immune responses in the lung. (author)

Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

DEFF Research Database (Denmark)

Heijerman, Harry; Westerman, Elsbeth; Conway, Steven

2009-01-01

, mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we...... review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics...

Preparation and Characterization of Azadirachtin Alginate-Biosorbent Based Formulations: Water Release Kinetics and Photodegradation Study.

Science.gov (United States)

Flores-Céspedes, Francisco; Martínez-Domínguez, Gerardo P; Villafranca-Sánchez, Matilde; Fernández-Pérez, Manuel

2015-09-30

The botanical insecticide azadirachtin was incorporated in alginate-based granules to obtain controlled release formulations (CRFs). The basic formulation [sodium alginate (1.47%) - azadirachtin (0.28%) - water] was modified by the addition of biosorbents, obtaining homogeneous hybrid hydrogels with high azadirachtin entrapment efficiency. The effect on azadirachtin release rate caused by the incorporation of biosorbents such as lignin, humic acid, and olive pomace in alginate formulation was studied by immersion of the granules in water under static conditions. The addition of the biosorbents to the basic alginate formulation reduces the rate of release because the lignin-based formulation produces a slower release. Photodegradation experiments showed the potential of the prepared formulations in protecting azadirachtin against simulated sunlight, thus improving its stability. The results showed that formulation prepared with lignin provided extended protection. Therefore, this study provides a new procedure to encapsulate the botanical insecticide azadirachtin, improving its delivery and photostability.

Inhalants

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... uses inhalants may be unable to learn new things or may have a hard time carrying on simple conversations. If the cerebral ... get drugs on the street, it is really hard to know what you get, Sometimes, ... put in, all sorts of things could happen. And other times, one might get ...

Radiation dose estimates and hazard evaluations for inhaled airborne radionuclides. Annual progress report, July 1980-June 1981

International Nuclear Information System (INIS)

Mewhinney, J.A.

1982-04-01

The objective of this project is to conduct confirmatory research on aerosol characteristics and the resulting radiation dose distribution in animals following inhalation and to provide prediction of health consequences in humans due to airborne radioactivity which might be released in normal operations or under accident conditions during production of nuclear fuel composed of mixed oxides of U and Pu. Four research reports summarize the results of specific areas of research being conducted. The first presents final results for several types of physical chemical characterization accomplished on samples of aerosols collected at an industrial facility during normal fabrication of mixed oxide fuel. Many of these characterizations were also done on aerosol samples collected during animal inhalation exposure procedures for biological studies using these aerosol materials. The second paper reports on the methods development process used for establishing a capability for measurement of the specific surface area of aerosols, an important determinant in the rate of dissolution of particulates deposited in lung. The third paper provides updated information on the retention, distribution and excretion of Pu after inhalation by Beagles of aerosols of either 750 0 C treated UO 2 + PuO 2 , 1750 0 C treated (U,Pu)O 2 or 850 0 C treated pure PuO 2 . This paper also reports the results of the formulation of a biomathematical model useful in describing the results of these three inhalation studies. The fourth paper describes the early results from two studies in which Fischer-344 rats received inhalation exposure to aerosols of (U,Pu)O 2 or pure PuO 2 to determine the relationship of radiation dose to biological response

Is the 'blue' colour convention for inhaled reliever medications important? A UK-based survey of healthcare professionals and patients with airways disease.

Science.gov (United States)

Fletcher, Monica; Scullion, Jane; White, John; Thompson, Bronwen; Capstick, Toby

2016-11-03

In many countries, short-acting β 2 -agonist inhalers have traditionally been coloured blue. This inhaled therapy has also conventionally been known as a 'reliever' by patients and healthcare professionals (HCPs), in comparison with 'preventer' medications (inhaled steroids). With the rapidly changing market in inhaled therapy for COPD and asthma and growing numbers of devices, there has been some concern that the erosion of traditional colour conventions is leading to patients (and HCPs) becoming confused about the role of different therapies. In order to assess whether there was concern over the perceived changing colour conventions, the UK Inhaler Group carried out a large online survey of patients and HCPs. The aim was to determine how patients and HCPS identify and describe inhaled drugs, and how this might impact on use of medicines and safety. The results of the survey highlighted the importance of the term 'blue inhaler' for patients with only 11.3% never referring to the colour when referring to their inhaler. For HCPs, 95% felt colour conventions were important when referring to reliever medication. In addition, HCPs appear to refer to inhalers mainly by colour when talking to patients. Our conclusions were that the concept of a 'blue inhaler' remains important to patients and healthcare professionals. These results add to the debate about the need to formalise the colour coding of inhaled therapies, in particular using the colour blue for inhalers for rapid relief of symptoms, as this convention may be an important measure and contributor to patient safety. Our survey should provide impetus for all interested parties to discuss and agree a formal industry-wide approach to colour coding of inhaled therapies for the benefit of patients and carers and HCPs.

Inhaled actinides: some safety issues and some research problems

International Nuclear Information System (INIS)

Bair, W.J.

1978-01-01

The following topics are discussed: limited research funds; risk coefficients for inhaled particles; the hot particle hypothesis; the Gofman-Martell contention; critical tissues for inhaled actinides inhalation hazards associated with future nuclear fuel cycles; and approach to be used by the inhalation panel

Evaluation of Topical Gel Bases Formulated with Various Essential ...

African Journals Online (AJOL)

Evaluation of Topical Gel Bases Formulated with Various Essential Oils for Antibacterial Activity against Methicillin- Resistant Staphylococcus Aureus. ... Lemon grass and thyme oils were chosen for further studies, including analysis of their composition by gas chromatography–mass spectrometry (GC/MS). Gels were ...

Investigation into Alternative Sugars as Potential Carriers for Dry Powder Formulation of Budesonide

Directory of Open Access Journals (Sweden)

Ali Nokhodchi

2011-08-01

Full Text Available Introduction: Dry powder inhaler (DPI formulations are so far being used for pulmonary drug delivery, mainly for the treatment of asthma and chronic obstructive pulmonary disease (COPD. Currently most of DPI formulations rely on lactose as a carrier in the drug powder blend. However, due to reducing sugar function of lactose which makes it incompatible with some drugs such as budesonide, it is realistic to investigate for alternative sugars that would overcome the concerned drawback but still have the positive aspects of lactose. Methods: The study was conducted by characterizing carriers for their physico-chemical properties and preparing drug/carrier blends with concentration of 5% and 10% drug with the carrier. The mixing uniformity (homogeneity of Budesonide in the blends was analyzed using spectrophotometer. The blend was then filled into NB7/2 Airmax inhaler device and the deposition profiles of the drug were determined using multi stage liquid impinger (MSLI after aerosolization at 4 kPa via the inhaler. The morphology of the carriers conducted using the scanning electron microscope. Results: The results determined that the mean fine particle fraction (FPF of 5% and 10% blends of mannitol was 61%, possibly due to fine elongated particles. Dextrose exhibited excellent flowability. Scanning electron microscope illustrated mannitol with fine elongated particles and dextrose presenting larger and coarse particles. It was found out that type of carriers, particle size distribution, and morphology would influence the FPF of budesonide. Conclusion: It may be concluded that mannitol could be suitable as a carrier on the basis of its pharmaceutical performance and successful achievement of FPF whereas the more hygroscopic sugars such as sorbitol or xylitol showed poor dispersibility leading to lower FPF.

Sex-based differences in lymphocyte proliferation in the spleen after vanadium inhalation.

Science.gov (United States)

Rodriguez-Lara, Vianey; Muñiz-Rivera Cambas, Angelica; González Villalva, Adriana; Fortoul, Teresa I

2016-07-01

Vanadium (V) is a transition metal often adhered to particulate matter and released into the atmosphere as vanadium pentoxide (V2O5) by the burning of fossil fuels. This air pollutant causes adverse effects in the immune system. Lymphocytosis and splenomegaly have been reported with increased white pulp in mice after V inhalation. The effect of V on the immune system as related to sex has been poorly investigated. This study sought to determine if V inhalation (a) produced lymphoproliferation that could explain the changes previously observed in the spleen and in peripheral blood lymphocyte counts and (b) whether any observed effects differed due to gender. Immunohistochemical analyses of Ki-67, a specific proliferation marker, was made in the spleens of CD-1 male and female mice exposed for 1 h, twice a week, over a 12-week period to V2O5 (at 1.4 mg V2O5/m(3)) by whole-body inhalation; similar analyses were performed on spleens of control mice exposed to vehicle (filtered air). The results showed that in male mice there was a significant increase in percentage of Ki-67 immunopositive lymphocytes starting from the second week and until the end of the exposure. The Ki-67 signal was cytoplasmic and nuclear in the exposed males, while in controls the signal was only nuclear. In female mice, V inhalation singificantly increased the percentage of proliferating lymphocytes only after 1 week of exposure. Ki-67 signal was observed only in the nucleus of lymphocytes from the control and exposed females. The results here help to explain the splenomegaly and lymphocytosis observed previously in male mice and support the lymphoproliferative effect induced by V. Lastly, the finding that there was a sex difference in the effect of vanadium on lymphocyte proliferation suggests a role for sex hormones in potential protection against V immunotoxicity; however, further studies are needed to support this hypothesis.

A geometrically exact beam element based on the absolute nodal coordinate formulation

International Nuclear Information System (INIS)

Gerstmayr, Johannes; Matikainen, Marko K.; Mikkola, Aki M.

2008-01-01

In this study, Reissner's classical nonlinear rod formulation, as implemented by Simo and Vu-Quoc by means of the large rotation vector approach, is implemented into the framework of the absolute nodal coordinate formulation. The implementation is accomplished in the planar case accounting for coupled axial, bending, and shear deformation. By employing the virtual work of elastic forces similarly to Simo and Vu-Quoc in the absolute nodal coordinate formulation, the numerical results of the formulation are identical to those of the large rotation vector formulation. It is noteworthy, however, that the material definition in the absolute nodal coordinate formulation can differ from the material definition used in Reissner's beam formulation. Based on an analytical eigenvalue analysis, it turns out that the high frequencies of cross section deformation modes in the absolute nodal coordinate formulation are only slightly higher than frequencies of common shear modes, which are present in the classical large rotation vector formulation of Simo and Vu-Quoc, as well. Thus, previous claims that the absolute nodal coordinate formulation is inefficient or would lead to ill-conditioned finite element matrices, as compared to classical approaches, could be refuted. In the introduced beam element, locking is prevented by means of reduced integration of certain parts of the elastic forces. Several classical large deformation static and dynamic examples as well as an eigenvalue analysis document the equivalence of classical nonlinear rod theories and the absolute nodal coordinate formulation for the case of appropriate material definitions. The results also agree highly with those computed in commercial finite element codes

Ivermectin disposition kinetics after subcutaneous and intramuscular administration of an oil-based formulation to cattle.

Science.gov (United States)

Lifschitz, A; Virkel, G; Pis, A; Imperiale, F; Sanchez, S; Alvarez, L; Kujanek, R; Lanusse, C

1999-10-01

Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activity of endectocide compounds. This work reports on the disposition kinetics and plasma availability of ivermectin (IVM) after subcutaneous (SC) and intramuscular (IM) administration as an oil-based formulation to cattle. Parasite-free Aberdeen Angus calves (n = 24; 240-280 kg) were divided into three groups (n = 8) and treated (200 microg/kg) with either an IVM oil-based pharmaceutical preparation (IVM-TEST formulation) (Bayer Argentina S.A.) given by subcutaneous (Group A) and intramuscular (Group B) injections or the IVM-CONTROL (non-aqueous formulation) (Ivomec, MSD Agvet) subcutaneously administered (Group C). Blood samples were taken over 35 days post-treatment and the recovered plasma was extracted and analyzed by HPLC using fluorescence detection. IVM was detected in plasma between 12 h and 35 days post-administration of IVM-TEST (SC and IM injections) and IVM-CONTROL formulations. Prolonged IVM absorption half-life (p oil-based formulation examined in this trial, compared to the standard preparation, may positively impact on its strategic use in cattle.

Workplace Inhalant Abuse in Adult Female: Brief Report

Directory of Open Access Journals (Sweden)

Rohit Verma

2011-01-01

Full Text Available Inhalant abuse is the purposeful inhalation of intoxicating gases and vapors for the purpose of achieving an altered mental state. With its propensity for being yet an under-recognized form of substance use, being gateway to hard substances, cross-cultural penetration crossing socioeconomic boundaries, and causing significant morbidity and mortality in early ages, the prevention of inhalant misuse is a highly pertinent issue. This clinical report identifies a newer perspective in the emergence of inhalant abuse initiation. We report a case of an adult female with late onset of inhalant dependence developing at workplace and recommend for greater awareness, prevention, and management of this expanding substance abuse problem.

Measurements and prediction of inhaled air quality with personalized ventilation

DEFF Research Database (Denmark)

Cermak, Radim; Majer, M.; Melikov, Arsen Krikor

2002-01-01

the room air) at flow rates ranging from less than 5 L/s up to 23 L/s. The air quality assessment was based on temperature measurements of the inhaled air and on the portion of the personalized air inhaled. The percentage of dissatisfied with the air quality was predicted. The results suggest......This paper examines the performance of five different air terminal devices for personalized ventilation in relation to the quality of air inhaled by a breathing thermal manikin in a climate chamber. The personalized air was supplied either isothermally or non-isothermally (6 deg.C cooler than...... that regardless of the temperature combinations, personalized ventilation may decrease significantly the number of occupants dissatisfied with the air quality. Under non-isothermal conditions the percentage of dissatisfied may decrease up to 4 times....

Formulating informative, data-based priors for failure probability estimation in reliability analysis

International Nuclear Information System (INIS)

Guikema, Seth D.

2007-01-01

Priors play an important role in the use of Bayesian methods in risk analysis, and using all available information to formulate an informative prior can lead to more accurate posterior inferences. This paper examines the practical implications of using five different methods for formulating an informative prior for a failure probability based on past data. These methods are the method of moments, maximum likelihood (ML) estimation, maximum entropy estimation, starting from a non-informative 'pre-prior', and fitting a prior based on confidence/credible interval matching. The priors resulting from the use of these different methods are compared qualitatively, and the posteriors are compared quantitatively based on a number of different scenarios of observed data used to update the priors. The results show that the amount of information assumed in the prior makes a critical difference in the accuracy of the posterior inferences. For situations in which the data used to formulate the informative prior is an accurate reflection of the data that is later observed, the ML approach yields the minimum variance posterior. However, the maximum entropy approach is more robust to differences between the data used to formulate the prior and the observed data because it maximizes the uncertainty in the prior subject to the constraints imposed by the past data

Exubera. Inhale therapeutic systems.

Science.gov (United States)

Bindra, Sanjit; Cefalu, William T

2002-05-01

Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations. 5. Lipolysis of Representative Formulations by Gastric Lipase

DEFF Research Database (Denmark)

Bakala-N'Goma, Jean-Claude; Williams, Hywel D.; Sassene, Philip J.

2015-01-01

Purpose Lipid-based formulations (LBF) are substrates for digestive lipases and digestion can significantly alter their properties and potential to support drug absorption. LBFs have been widely examined for their behaviour in the presence of pancreatic enzymes. Here, the impact of gastric lipase...... on the digestion of representative formulations from the Lipid Formulation Classification System has been investigated. Methods The pHstat technique was used to measure the lipolysis by recombinant dog gastric lipase (rDGL) of eight LBFs containing either medium (MC) or long (LC) chain triglycerides and a range...

Faraday instability-based micro droplet ejection for inhalation drug delivery

Science.gov (United States)

Tsai, C.S.; Mao, R.W.; Lin, S.K.; Zhu, Y.; Tsai, S.C.

2014-01-01

We report here the technology and the underlying science of a new device for inhalation (pulmonary) drug delivery which is capable of fulfilling needs unmet by current commercial devices. The core of the new device is a centimeter-size clog-free silicon-based ultrasonic nozzle with multiple Fourier horns in resonance at megahertz (MHz) frequency. The dramatic resonance effect among the multiple horns and high growth rate of the MHz Faraday waves excited on a medicinal liquid layer together facilitate ejection of monodisperse droplets of desirable size range (2–5 µm) at low electrical drive power (<1.0 W). The small nozzle requiring low drive power has enabled realization of a pocket-size (8.6 × 5.6 × 1.5 cm3) ultrasonic nebulizer. A variety of common pulmonary drugs have been nebulized using the pocket-size unit with desirable aerosol sizes and output rate. These results clearly provide proof-of-principle for the new device and confirm its potential for commercialization. PMID:25045720

An adhesive contact mechanics formulation based on atomistically induced surface traction

Energy Technology Data Exchange (ETDEWEB)

Fan, Houfu [Department of Civil and Environmental Engineering, University of California, Berkeley, CA 94720 (United States); Ren, Bo [Livermore Software Technology Corporation, 7374 Las Positas Road, Livermore, CA 94551 (United States); Li, Shaofan, E-mail: shaofan@berkeley.edu [Department of Civil and Environmental Engineering, University of California, Berkeley, CA 94720 (United States)

2015-12-01

In this work, we have developed a novel multiscale computational contact formulation based on the generalized Derjuguin approximation for continua that are characterized by atomistically enriched constitutive relations in order to study macroscopic interaction between arbitrarily shaped deformable continua. The proposed adhesive contact formulation makes use of the microscopic interaction forces between individual particles in the interacting bodies. In particular, the double-layer volume integral describing the contact interaction (energy, force vector, matrix) is converted into a double-layer surface integral through a mathematically consistent approach that employs the divergence theorem and a special partitioning technique. The proposed contact model is formulated in the nonlinear continuum mechanics framework and implemented using the standard finite element method. With no large penalty constant, the stiffness matrix of the system will in general be well-conditioned, which is of great significance for quasi-static analysis. Three numerical examples are presented to illustrate the capability of the proposed method. Results indicate that with the same mesh configuration, the finite element computation based on the surface integral approach is faster and more accurate than the volume integral based approach. In addition, the proposed approach is energy preserving even in a very long dynamic simulation.

The Advantages of Low-Flow Inhalational Anesthesia

Directory of Open Access Journals (Sweden)

P. Torok

2005-01-01

Full Text Available The paper deals with the economical and ecological use of inhalation anesthetics in low-flow anesthesia (LFA, 1—0.5 l/ min and high-flow anesthesia (HFA, more than 2—6 l/min. Four hundred and ninety six inhalational anesthesias lasting at least 80 minutes were analyzed in each group under consideration. The concentration of inhalation anesthetics was measures in the atmosphere of an operative theatre if inhalational anesthesia lasted more than 4 hours. There is evidence for the economical and ecological benefits in the use of LFA in terms of the availability of appropriate anesthesiological equipment, monitoring, and a highly skilled anesthesiologist.

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

Directory of Open Access Journals (Sweden)

Tongtong Zhang

2018-05-01

Full Text Available 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. Key words: Curcumin, Dry powder inhaler, Liposome, Primary lung cancer, Pulmonary delivery

Estimation of inhaled airborne particle number concentration by subway users in Seoul, Korea

International Nuclear Information System (INIS)

Kim, Minhae; Park, Sechan; Namgung, Hyeong-Gyu; Kwon, Soon-Bark

2017-01-01

Exposure to airborne particulate matter (PM) causes several diseases in the human body. The smaller particles, which have relatively large surface areas, are actually more harmful to the human body since they can penetrate deeper parts of the lungs or become secondary pollutants by bonding with other atmospheric pollutants, such as nitrogen oxides. The purpose of this study is to present the number of PM inhaled by subway users as a possible reference material for any analysis of the hazards to the human body arising from the inhalation of such PM. Two transfer stations in Seoul, Korea, which have the greatest number of users, were selected for this study. For 0.3–0.422 μm PM, particle number concentration (PNC) was highest outdoors but decreased as the tester moved deeper underground. On the other hand, the PNC between 1 and 10 μm increased as the tester moved deeper underground and showed a high number concentration inside the subway train as well. An analysis of the particles to which subway users are actually exposed to (inhaled particle number), using particle concentration at each measurement location, the average inhalation rate of an adult, and the average stay time at each location, all showed that particles sized 0.01–0.422 μm are mostly inhaled from the outdoor air whereas particles sized 1–10 μm are inhaled as the passengers move deeper underground. Based on these findings, we expect that the inhaled particle number of subway users can be used as reference data for an evaluation of the hazards to health caused by PM inhalation. - Highlights: • Size-dependent aerosol number was measured along the path of subway user. • Particles less than 0.4 μm were inhaled in outdoor but less so as deeper underground. • Coarse particles were inhaled significantly as users moved deeper underground. - We estimated the inhaled aerosol number concentration depending on particle size along the path of subway users.

Inhaler devices - from theory to practice

DEFF Research Database (Denmark)

Sanchis, Joaquin; Corrigan, Chris; Levy, Mark L

2013-01-01

This brief overview of the factors determining lung deposition of aerosols provides background information required by health care providers when instructing patients to use their prescribed inhalers. We discuss differences in the optimal inhalation manoeuvres for each type of aerosol generator a...

Novel Budesonide Particles for Dry Powder Inhalation Prepared Using a Microfluidic Reactor Coupled With Ultrasonic Spray Freeze Drying.

Science.gov (United States)

Saboti, Denis; Maver, Uroš; Chan, Hak-Kim; Planinšek, Odon

2017-07-01

Budesonide (BDS) is a potent active pharmaceutical ingredient, often administered using respiratory devices such as metered dose inhalers, nebulizers, and dry powder inhalers. Inhalable drug particles are conventionally produced by crystallization followed by milling. This approach tends to generate partially amorphous materials that require post-processing to improve the formulations' stability. Other methods involve homogenization or precipitation and often require the use of stabilizers, mostly surfactants. The purpose of this study was therefore to develop a novel method for preparation of fine BDS particles using a microfluidic reactor coupled with ultrasonic spray freeze drying, and hence avoiding the need of additional homogenization or stabilizer use. A T-junction microfluidic reactor was employed to produce particle suspension (using an ethanol-water, methanol-water, and an acetone-water system), which was directly fed into an ultrasonic atomization probe, followed by direct feeding to liquid nitrogen. Freeze drying was the final preparation step. The result was fine crystalline BDS powders which, when blended with lactose and dispersed in an Aerolizer at 100 L/min, generated fine particle fraction in the range 47.6% ± 2.8% to 54.9% ± 1.8%, thus exhibiting a good aerosol performance. Subsequent sample analysis confirmed the suitability of the developed method to produce inhalable drug particles without additional homogenization or stabilizers. The developed method provides a viable solution for particle isolation in microfluidics in general. Copyright © 2017 American Pharmacists Association®. All rights reserved.

Development of a Rational Design Space for Optimizing Mixing Conditions for Formation of Adhesive Mixtures for Dry-Powder Inhaler Formulations.

Science.gov (United States)

Sarkar, Saurabh; Minatovicz, Bruna; Thalberg, Kyrre; Chaudhuri, Bodhisattwa

2017-01-01

The purpose of the present study was to develop guidance toward rational choice of blenders and processing conditions to make robust and high performing adhesive mixtures for dry-powder inhalers and to develop quantitative experimental approaches for optimizing the process. Mixing behavior of carrier (LH100) and AstraZeneca fine lactose in high-shear and low-shear double cone blenders was systematically investigated. Process variables impacting the mixing performance were evaluated for both blenders. The performance of the blenders with respect to the mixing time, press-on forces, static charging, and abrasion of carrier fines was monitored, and for some of the parameters, distinct differences could be detected. A comparison table is presented, which can be used as a guidance to enable rational choice of blender and process parameters based on the user requirements. Segregation of adhesive mixtures during hopper discharge was also investigated. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

Science.gov (United States)

Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

2015-05-01

The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species. © 2014 Society for Risk Analysis.

Formulants of glyphosate-based herbicides have more deleterious impact than glyphosate on TM4 Sertoli cells.

Science.gov (United States)

Vanlaeys, Alison; Dubuisson, Florine; Seralini, Gilles-Eric; Travert, Carine

2018-05-15

Roundup and Glyphogan are glyphosate-based herbicides containing the same concentration of glyphosate and confidential formulants. Formulants are declared as inert diluents but some are more toxic than glyphosate, such as the family of polyethoxylated alkylamines (POEA). We tested glyphosate alone, glyphosate-based herbicide formulations and POEA on the immature mouse Sertoli cell line (TM4), at concentrations ranging from environmental to agricultural-use levels. Our results show that formulations of glyphosate-based herbicides induce TM4 mitochondrial dysfunction (like glyphosate, but to a lesser extent), disruption of cell detoxification systems, lipid droplet accumulation and mortality at sub-agricultural doses. Formulants, especially those present in Glyphogan, are more deleterious than glyphosate and thus should be considered as active principles of these pesticides. Lipid droplet accumulation after acute exposure to POEA suggests the rapid penetration and accumulation of formulants, leading to mortality after 24 h. As Sertoli cells are essential for testicular development and normal onset of spermatogenesis, disturbance of their function by glyphosate-based herbicides could contribute to disruption of reproductive function demonstrated in mammals exposed to these pesticides at a prepubertal stage of development. Copyright © 2017. Published by Elsevier Ltd.

Formulation D'Aliments Infantiles a Base De Farines D'Igname ...

African Journals Online (AJOL)

However, formulated flours were poor in calcium, iron and zinc. ... The results obtained show that, swelling power and solubility decreased with the rate of soy incorporated. In addition, phenolic compounds of fortified yam based flours with soy, ...

Long-term effects of aluminium dust inhalation.

Science.gov (United States)

Peters, Susan; Reid, Alison; Fritschi, Lin; de Klerk, Nicholas; Musk, A W Bill

2013-12-01

During the 1950s and 1960s, aluminium dust inhalation was used as a potential prophylaxis against silicosis in underground miners, including in Australia. We investigated the association between aluminium dust inhalation and cardiovascular, cerebrovascular and Alzheimer's diseases in a cohort of Australian male underground gold miners. We additionally looked at pneumoconiosis mortality to estimate the effect of the aluminium therapy. SMRs and 95% CI were calculated to compare mortality of the cohort members with that of the Western Australian male population (1961-2009). Internal comparisons on duration of aluminium dust inhalation were examined using Cox regression. Aluminium dust inhalation was reported for 647 out of 1894 underground gold miners. During 42 780 person-years of follow-up, 1577 deaths were observed. An indication of increased mortality of Alzheimer's disease among miners ever exposed to aluminium dust was found (SMR=1.38), although it was not statistically significant (95% CI 0.69 to 2.75). Rates for cardiovascular and cerebrovascular death were above population levels, but were similar for subjects with or without a history of aluminium dust inhalation. HRs suggested an increasing risk of cardiovascular disease with duration of aluminium dust inhalation (HR=1.02, 95% CI 1.00 to 1.04, per year of exposure). No difference in the association between duration of work underground and pneumoconiosis was observed between the groups with or without aluminium dust exposure. No protective effect against silicosis was observed from aluminium dust inhalation. Conversely, exposure to aluminium dust may possibly increase the risk of cardiovascular disease and dementia of the Alzheimer's type.

Assessing inhalation injury in the emergency room

Directory of Open Access Journals (Sweden)

Tanizaki S

2015-07-01

Full Text Available Shinsuke Tanizaki Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan Abstract: Respiratory tract injuries caused by inhalation of smoke or chemical products are related to significant morbidity and mortality. While many strategies have been built up to manage cutaneous burn injuries, few logical diagnostic strategies for patients with inhalation injuries exist and almost all treatment is supportive. The goals of initial management are to ensure that the airway allows adequate oxygenation and ventilation and to avoid ventilator-induced lung injury and substances that may complicate subsequent care. Intubation should be considered if any of the following signs exist: respiratory distress, stridor, hypoventilation, use of accessory respiratory muscles, blistering or edema of the oropharynx, or deep burns to the face or neck. Any patients suspected to have inhalation injuries should receive a high concentration of supplemental oxygen to quickly reverse hypoxia and to displace carbon monoxide from protein binding sites. Management of carbon monoxide and cyanide exposure in smoke inhalation patients remains controversial. Absolute indications for hyperbaric oxygen therapy do not exist because there is a low correlation between carboxyhemoglobin levels and the severity of the clinical state. A cyanide antidote should be administered when cyanide poisoning is clinically suspected. Although an ideal approach for respiratory support of patients with inhalation injuries do not exist, it is important that they are supported using techniques that do not further exacerbate respiratory failure. A well-organized strategy for patients with inhalation injury is critical to reduce morbidity and mortality. Keywords: inhalation injury, burn, carbon monoxide poisoning, cyanide poisoning

Inhaled plutonium oxide in dogs

International Nuclear Information System (INIS)

Anon.

1981-01-01

This project is concerned with long-term experiments to determine the life-span dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. The tissue distribution of plutonium, radiation effects in the lung and hematologic changes in plutonium-exposed beagles with lung tumors were evaluated

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 4

DEFF Research Database (Denmark)

Williams, Hywel D; Sassene, Philip; Kleberg, Karen

2014-01-01

The Lipid Formulation Classification System Consortium looks to develop standardized in vitro tests and to generate much-needed performance criteria for lipid-based formulations (LBFs). This article highlights the value of performing a second, more stressful digestion test to identify LBFs near...... a performance threshold and to facilitate lead formulation selection in instances where several LBF prototypes perform adequately under standard digestion conditions (but where further discrimination is necessary). Stressed digestion tests can be designed based on an understanding of the factors that affect LBF...... development, and facilitate dialogue with the regulatory authorities. This classification system is based on the concept that performance evaluations across three in vitro tests, designed to subject a LBF to progressively more challenging conditions, will enable effective LBF discrimination and performance...

49 CFR 172.555 - POISON INHALATION HAZARD placard.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition to...

Platelet lysate formulations based on mucoadhesive polymers for the treatment of corneal lesions.

Science.gov (United States)

Sandri, Giuseppina; Bonferoni, Maria Cristina; Rossi, Silvia; Ferrari, Franca; Mori, Michela; Del Fante, Claudia; Perotti, Cesare; Scudeller, Luigia; Caramella, Carla

2011-02-01

Growth factors contained in platelet α-granules initiate and modulate tissue repair and are proposed for the treatment of soft and hard-tissue surgical conditions and in the management of non-healing wounds. Platelet lysate is a hemoderivative obtained from platelet-rich plasma and is capable of releasing a pool of growth factors. Many medical and surgical techniques have been proposed for the treatment of corneal lesions; management of these conditions remains problematic and healing with standard protocols is unattainable. The aim of this study was to develop formulations suitable for prolonging the contact of platelet lysate with the damaged cornea for the time necessary to exert a therapeutic effect. Two vehicles, one based on polyacrylic acid and one based on chitosan, were autoclaved and loaded with platelet lysate and the resultant formulations were characterized for rheology, mucoadhesion, vehicle compatibility and stability. The proliferation effect was tested on two cell culture types (rabbit corneal epithelial cells and fibroblasts). An in-vitro wound-healing test was performed on fibroblasts. In both cases the formulations were compared with platelet lysate diluted with saline at the same concentration. Both formulations maintained the rheological and mucoadhesive properties of the vehicles and the proliferative activity of platelet lysate. The chitosan formulation was able to significantly enhance epithelial cell growth even after storage of up to 2 weeks (in-use conditions), while the polyacrylic acid formulation was less efficient, probably due to the characteristics of the cell model used. The in-vitro wound-healing test performed on fibroblasts confirmed the differences between the two vehicles. The effect induced by the platelet lysate and chitosan formulation was faster than that of the polyacrylic acid formulation and complete in-vitro wound repair was achieved within 48 h. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society.

49 CFR 172.429 - POISON INHALATION HAZARD label.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to complying...

Evaluation of soy-based surface active copolymers as surfactant ingredients in model shampoo formulations.

Science.gov (United States)

Popadyuk, A; Kalita, H; Chisholm, B J; Voronov, A

2014-12-01

A new non-toxic soybean oil-based polymeric surfactant (SBPS) for personal-care products was developed and extensively characterized, including an evaluation of the polymeric surfactant performance in model shampoo formulations. To experimentally assure applicability of the soy-based macromolecules in shampoos, either in combination with common anionic surfactants (in this study, sodium lauryl sulfate, SLS) or as a single surface-active ingredient, the testing of SBPS physicochemical properties, performance and visual assessment of SBPS-based model shampoos was carried out. The results obtained, including foaming and cleaning ability of model formulations, were compared to those with only SLS as a surfactant as well as to SLS-free shampoos. Overall, the results show that the presence of SBPS improves cleaning, foaming, and conditioning of model formulations. SBPS-based formulations meet major requirements of multifunctional shampoos - mild detergency, foaming, good conditioning, and aesthetic appeal, which are comparable to commercially available shampoos. In addition, examination of SBPS/SLS mixtures in model shampoos showed that the presence of the SBPS enables the concentration of SLS to be significantly reduced without sacrificing shampoo performance. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Formulation and Characterization of ADN-Based Liquid Monopropellants

Science.gov (United States)

Wingborg, N.; Eldsäter, C.; Skifs, H.

2004-10-01

Ternary ionic solutions are promising green propellants to replace monopropellant hydrazine. Ammonium dinitramide, ADN, is well suited as oxidizer in these propellants due to its high solubility. This paper presents the formulation of different ADN-based liquid monopropellants and the characterization of their properties such as stability, density, viscosity and sensitivity. To be able to use ADN-based monopropellants for propulsion applications, ADN must be produced in a way to minimize the effect on the environment and in sufficient quantities. This paper thus also briefly presents the industrial production of ADN in Sweden and the efforts made to optimize the process.

Chemicals-Based Formulation Design: Virtual Experimentations

DEFF Research Database (Denmark)

Conte, Elisa; Gani, Rafiqul

2011-01-01

This paper presents a systematic procedure for virtual experimentations related to the design of liquid formulated products. All the experiments that need to be performed when designing a liquid formulated product (lotion), such as ingredients selection and testing, solubility tests, property mea...... on the design of an insect repellent lotion will show that the software is an essential instrument in decision making, and that it reduces time and resources since experimental efforts can be focused on one or few product alternatives....

Estimation of inhaled airborne particle number concentration by subway users in Seoul, Korea.

Science.gov (United States)

Kim, Minhae; Park, Sechan; Namgung, Hyeong-Gyu; Kwon, Soon-Bark

2017-12-01

Exposure to airborne particulate matter (PM) causes several diseases in the human body. The smaller particles, which have relatively large surface areas, are actually more harmful to the human body since they can penetrate deeper parts of the lungs or become secondary pollutants by bonding with other atmospheric pollutants, such as nitrogen oxides. The purpose of this study is to present the number of PM inhaled by subway users as a possible reference material for any analysis of the hazards to the human body arising from the inhalation of such PM. Two transfer stations in Seoul, Korea, which have the greatest number of users, were selected for this study. For 0.3-0.422 μm PM, particle number concentration (PNC) was highest outdoors but decreased as the tester moved deeper underground. On the other hand, the PNC between 1 and 10 μm increased as the tester moved deeper underground and showed a high number concentration inside the subway train as well. An analysis of the particles to which subway users are actually exposed to (inhaled particle number), using particle concentration at each measurement location, the average inhalation rate of an adult, and the average stay time at each location, all showed that particles sized 0.01-0.422 μm are mostly inhaled from the outdoor air whereas particles sized 1-10 μm are inhaled as the passengers move deeper underground. Based on these findings, we expect that the inhaled particle number of subway users can be used as reference data for an evaluation of the hazards to health caused by PM inhalation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Field efficacy of inorganic carrier based formulations of Serratia ...

African Journals Online (AJOL)

On the basis of the result of this experiment, it can be recommended that vermiculite (80 g/100 g of product) based formulation of S. entomophila AB2 applied at 3.6 qt hec-1 in sesame could be an effective measure of lepidopteron pest control as well as biofertilizer for qualitative and quantitative increase of sesame.

Evaluation of Inhaler Techniques Among Asthma Patients Seen in ...

African Journals Online (AJOL)

hanumantp

Drug inhalation is an important and a common mode of .... to evaluate the use of inhaler technique among asthma patients in a .... The median duration of the use of the inhalers is 24 ..... Scalabrini A, Cukier A. Incorrect application technique of.

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3

DEFF Research Database (Denmark)

Williams, Hywel D; Sassene, Philip; Kleberg, Karen

2013-01-01

PURPOSE: Recent studies have shown that digestion of lipid-based formulations (LBFs) can stimulate both supersaturation and precipitation. The current study has evaluated the drug, formulation and dose-dependence of the supersaturation - precipitation balance for a range of LBFs. METHODS: Type I,...

Assessment of inhalation risk due to radioactivity released from coal-based thermal power plant

International Nuclear Information System (INIS)

Sahu, S.K.; Pandit, G.G.; Shukla, V.K.; Puranik, V.D.; Kushwaha, H.S.

2006-01-01

In India, the coal based thermal power plants have been the major source of power generation in the past and would continue for decades to come. As the coal contains naturally occurring primordial radionuclides the burning of pulverized coal to produce energy for generation of electricity in thermal power plants will result in the emission of a variety of natural radioactive elements into the environment in the vicinity of thermal power plants. In this paper we have used two different methods for characterization of uncertainty in inhalation risk to the general public around 10 Kms radius in the neighborhood of a coal-fired thermal power plant. (author)

Recommendations of the Oligonucleotide Safety Working Group's Formulated Oligonucleotide Subcommittee for the Safety Assessment of Formulated Oligonucleotide-Based Therapeutics.

Science.gov (United States)

Marlowe, Jennifer L; Akopian, Violetta; Karmali, Priya; Kornbrust, Douglas; Lockridge, Jennifer; Semple, Sean

2017-08-01

The use of lipid formulations has greatly improved the ability to effectively deliver oligonucleotides and has been instrumental in the rapid expansion of therapeutic development programs using oligonucleotide drugs. However, the development of such complex multicomponent therapeutics requires the implementation of unique, scientifically sound approaches to the nonclinical development of these drugs, based upon a hybrid of knowledge and experiences drawn from small molecule, protein, and oligonucleotide therapeutic drug development. The relative paucity of directly applicable regulatory guidance documents for oligonucleotide therapeutics in general has resulted in the generation of multiple white papers from oligonucleotide drug development experts and members of the Oligonucleotide Safety Working Group (OSWG). The members of the Formulated Oligonucleotide Subcommittee of the OSWG have utilized their collective experience working with a variety of formulations and their associated oligonucleotide payloads, as well as their insights into regulatory considerations and expectations, to generate a series of consensus recommendations for the pharmacokinetic characterization and nonclinical safety assessment of this unique class of therapeutics. It should be noted that the focus of Subcommittee discussions was on lipid nanoparticle and other types of particulate formulations of therapeutic oligonucleotides and not on conjugates or other types of modifications of oligonucleotide structure intended to facilitate delivery.

Personal exposure to inhalable cement dust among construction workers.

Science.gov (United States)

Peters, Susan; Thomassen, Yngvar; Fechter-Rink, Edeltraud; Kromhout, Hans

2009-01-01

Objective- A case study was carried out to assess cement dust exposure and its determinants among construction workers and for comparison among workers in cement and concrete production.Methods- Full-shift personal exposure measurements were performed and samples were analysed for inhalable dust and its cement content. Exposure variability was modelled with linear mixed models.Results- Inhalable dust concentrations at the construction site ranged from 0.05 to 34 mg/m(3), with a mean of 1.0 mg/m(3). Average concentration for inhalable cement dust was 0.3 mg/m(3) (GM; range 0.02-17 mg/m(3)). Levels in the ready-mix and pre-cast concrete plants were on average 0.5 mg/m(3) (GM) for inhalable dust and 0.2 mg/m(3) (GM) for inhalable cement dust. Highest concentrations were measured in cement production, particularly during cleaning tasks (inhalable dust GM = 55 mg/m(3); inhalable cement dust GM = 33 mg/m(3)) at which point the workers wore personal protective equipment. Elemental measurements showed highest but very variable cement percentages in the cement plant and very low percentages during reinforcement work and pouring. Most likely other sources were contributing to dust concentrations, particularly at the construction site. Within job groups, temporal variability in exposure concentrations generally outweighed differences in average concentrations between workers. 'Using a broom', 'outdoor wind speed' and 'presence of rain' were overall the most influential factors affecting inhalable (cement) dust exposure.Conclusion- Job type appeared to be the main predictor of exposure to inhalable (cement) dust at the construction site. Inhalable dust concentrations in cement production plants, especially during cleaning tasks, are usually considerably higher than at the construction site.

Slag-based saltstone formulations

International Nuclear Information System (INIS)

Langton, C.A.

1987-08-01

Approximately 400 x 10 6 L of low-level alkaline salt solution will be treated at the Savannah River Plant (SRP) Defense Waste Processing Facility (DWPF) prior to disposal in concrete vaults at SRP. Treatment involves removal of Cs + and Sr +2 , followed by solidification and stabilization of potential contaminants in saltstone, a hydrated ceramic wasteform. Chromium, technetium, and nitrate releases from saltstone can be significantly reduced by substituting hydraulic blast furnace slag for portland cement in the formulation designs. Slag-based mixes are also compatible with the Class F flyash used in saltstone as a functional extender to control heat of hydration and reduce permeability. (Class F flyash is also locally available at SRP.) A monolithic wasteform is produced by the hydration of the slag and flyash. Soluble ion release (NO 3- ) is controlled by the saltstone microstructure. Chromium and technetium are less leachable from slag mixes because these species are chemically reduced to a lower valence state by ferrous iron in the slag and are precipitated as relatively insoluble phases, such as Cr(OH) 3 and TcO 2 . 3 refs., 3 figs., 2 tabs

Respirable versus inhalable dust sampling

International Nuclear Information System (INIS)

Hondros, J.

1987-01-01

The ICRP uses a total inhalable dust figure as the basis of calculations on employee lung dose. This paper was written to look at one aspect of the Olympic Dam dust situation, namely, the inhalable versus respirable fraction of the dust cloud. The results of this study will determine whether it is possible to use respirable dust figures, as obtained during routine monitoring to help in the calculations of employee exposure to internal radioactive contaminants

Animal Testing for Acute Inhalation Toxicity: A Thing of the Past?

DEFF Research Database (Denmark)

Da Silva, Emilie; Sørli, Jorid Birkelund

2018-01-01

According to REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), testing for acute inhalation toxicity is required for chemicals manufactured or imported at tonnages ≥ 10 tons per year. Three OECD test guidelines for acute inhalation toxicity in vivo are adopted (TG 403......, TG 436, and TG 433). Since animal testing is ethically, scientifically and economically questionable, adoption of alternative methods by the European Union and the OECD is needed. An in vitro system based on the study of lung surfactant function is introduced....

Economic considerations in the use of inhaled anesthetic agents.

Science.gov (United States)

Golembiewski, Julie

2010-04-15

To describe the components of and factors contributing to the costs of inhaled anesthesia, basis for quantifying and comparing these costs, and practical strategies for performing pharmacoeconomic analyses and reducing the costs of inhaled anesthetic agents. Inhaled anesthesia can be costly, and some of the variable costs, including fresh gas flow rates and vaporizer settings, are potential targets for cost savings. The use of a low fresh gas flow rate maximizes rebreathing of exhaled anesthetic gas and is less costly than a high flow rate, but it provides less control of the level of anesthesia. The minimum alveolar concentration (MAC) hour is a measure that can be used to compare the cost of inhaled anesthetic agents at various fresh gas flow rates. Anesthesia records provide a sense of patterns of inhaled anesthetic agent use, but the amount of detail can be limited. Cost savings have resulted from efforts to reduce the direct costs of inhaled anesthetic agents, but reductions in indirect costs through shortened times to patient recovery and discharge following the judicious use of these agents are more difficult to demonstrate. The patient case mix, fresh gas flow rates typically used during inhaled anesthesia, availability and location of vaporizers, and anesthesia care provider preferences and practices should be taken into consideration in pharmacoeconomic evaluations and recommendations for controlling the costs of inhaled anesthesia. Understanding factors that contribute to the costs of inhaled anesthesia and considering those factors in pharmacoeconomic analyses and recommendations for use of these agents can result in cost savings.

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ...

The use of multiple respiratory inhalers requiring different inhalation techniques has an adverse effect on COPD outcomes

Directory of Open Access Journals (Sweden)

Bosnic-Anticevich S

2016-12-01

Full Text Available Sinthia Bosnic-Anticevich,1 Henry Chrystyn,2 Richard W Costello,3,4 Myrna B Dolovich,5 Monica J Fletcher,6 Federico Lavorini,7 Roberto Rodríguez-Roisin,8 Dermot Ryan,9,10 Simon Wan Yau Ming,2 David B Price2,11 1Woolcock Institute of Medical Research, School of Medical Sciences, University of Sydney and Sydney Local Health District, Sydney, NSW, Australia; 2Observational and Pragmatic Research Institute Pte Ltd, Singapore; 3RCSI Medicine, Royal College of Surgeons, 4RCSI Education & Research Centre, Beaumont Hospital, Beaumont, Dublin, Ireland; 5Department of Medicine, Respirology, McMaster University, ON, Canada; 6Education for Health, Warwick, UK; 7Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 8Respiratory Institute, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; 9Optimum Patient Care, Cambridge, 10Centre for Population Health Sciences, University of Edinburgh, Edinburgh, 11Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques. Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique. Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known. Aims: To compare clinical outcomes of COPD patients who use devices requiring similar inhalation technique with those who use devices with mixed techniques. Methods: A matched cohort design was used, with 2 years of data from the Optimum Patient Care Research Database. Matching variables were established from a baseline year of follow-up data, and two cohorts were formed: a “similar-devices cohort” and a “mixed-devices cohort”. COPD-related events were recorded during an outcome year of follow-up. The primary outcome measure was an

INDOOR AIR QUALITY AND INHALATION EXPOSURE - SIMULATION TOOL KIT

Science.gov (United States)

A Microsoft Windows-based indoor air quality (IAQ) simulation software package is presented. Named Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short, this package complements and supplements existing IAQ simulation programs and is desi...

Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease

NARCIS (Netherlands)

Sin, DD; Wu, L; Anderson, JA; Anthonisen, NR; Buist, AS; Burge, PS; Calverley, PM; Connett, JE; Lindmark, B; Pauwels, RA; Postma, DS; Soriano, JB; Szafranski, W; Vestbo, J

2005-01-01

Background: Clinical studies suggest that inhaled corticosteroids reduce exacerbations and improve health status in chronic obstructive pulmonary disease (COPD). However, their effect on mortality is unknown. Methods: A pooled analysis, based on intention to treat, of individual patient data from

Precipitation in Powder Metallurgy, Nickel Base Superalloys: Review of Modeling Approach and Formulation of Engineering (Postprint)

Science.gov (United States)

2016-12-01

AFRL-RX-WP-JA-2016-0333 PRECIPITATION IN POWDER- METALLURGY , NICKEL-BASE SUPERALLOYS: REVIEW OF MODELING APPROACH AND FORMULATION OF...PRECIPITATION IN POWDER- METALLURGY , NICKEL- BASE SUPERALLOYS: REVIEW OF MODELING APPROACH AND FORMULATION OF ENGINEERING (POSTPRINT) 5a...and kinetic parameters required for the modeling of γ′ precipitation in powder- metallurgy (PM), nickel-base superalloys are summarized. These

Development and evaluation of an inhalation chamber for in vivo tests

Directory of Open Access Journals (Sweden)

EDUARDO R. DA SILVA

2017-08-01

Full Text Available ABSTRACT The bioavailability, toxicity, and therapeutic efficacy of a drug is directly related to its administration route. The pulmonary route can be accessed by inhalation after fumigation, vaporization or nebulization. Thus, pharmacological and toxicological evaluation accessed by an apparatus specifically designed and validated for this type of administration is extremely important. Based on pre-existing models, an inhalation chamber was developed. This presents a central structure with five animal holders. The nebulized air passes directly and continuously through these holders and subsequently to an outlet. Evaluation of its operation was performed using clove essential oil, a nebulizer, and a flow meter. The air within the chamber was collected by static headspace and analyzed by gas chromatography with a flame ionization detector. For this purpose, a 2.5 minutes chromatographic method was developed. The air flow in each of the five outputs was 0.92 liters per minute. During the first minute, the chamber became saturated with the nebulized material. Homogeneous and continuous operation of the chamber was observed without accumulation of volatile material inside it for 25 minutes. The inhalation chamber works satisfactorily for in vivo tests with medicines designed to be administrated by inhalation.

Cromolyn Oral Inhalation

Science.gov (United States)

... your doctor.Cromolyn oral inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Your doctor will prescribe ...

Ipratropium Oral Inhalation

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... with the clear end pointing upward. Place the metal canister inside the clear end of the inhaler. ... do not discard it in an incinerator or fire.Unneeded medications should be disposed of in special ...

Inhaled Antibiotics in Reanimatology: Problem State and Development Prospects (Review

Directory of Open Access Journals (Sweden)

A. N. Kuzovlev

2017-01-01

Full Text Available Nosocomial pneumonia is the second most common nosocomial infection in critical care units and most common in ALV patients (9—27%. The purpose of this literature review is to discuss the latest domestic and foreign body of evidence concerning the use of inhaled antibiotics в critical care. Search for domestic publications (literature reviews, observation studies, double blind randomized studies was carried out in elibrary.ru database, for foreign — in PubMed. Database for the period of yrs. 2005—2017. The following search enquiries were used: «inhaled antibiotics», «nosocomial pneumonia», «inhaled tobramycin», «inhaled colistin». The analysis includes 67 publications of yrs. 2007—2017 and 1 publication of yr. 2000. The literature review includes drug descriptions, contemporary capabilities of inhaled antibiotic therapy for nosocomial pneumonia, the advantages and drawbacks of this method of treatment. Special attention is focused on the use of inhaled aminoglycosides and inhaled colistin during nosocomial pneumonia in critical care units.

New waste based clinkers: Belite and lime formulations

International Nuclear Information System (INIS)

Raupp-Pereira, Fabiano; Ball, Richard James; Rocha, Joao; Labrincha, Joao A.; Allen, Geoffrey C.

2008-01-01

This work describes the formulation of new belite-based (CR2) and lime-based (CR3) cementitious materials derived from industrial wastes, such as sludges (generated in the Al-anodising and surface coating industrial processes, potable water filtration/cleaning operations and in marble sawing processes) and foundry sand. Powder mixtures were prepared and fired at different temperatures. For comparison, similar formulations were prepared with pre-treated and commercially available natural raw materials and processed in similar conditions. The thermal process was followed by differential scanning calorimetry (DSC) and high-temperature powder X-ray diffraction (HT-XRD) studies. The CR2 clinker was found to contain belite as the main cementitious phase, the main polymorph being identified by NMR. The CR3 clinker contained common cementitious phases, such as C 3 A and C 3 S, but free lime and calcium aluminium oxide sulphates were also identified by high temperature XRD and NMR. Then the corresponding cement was prepared and the evolution of the mechanical strength with time was evaluated. The lime-based cement obtained from wastes shows a stronger hardening character than the standard material, which tends to show dusting phenomena due to the presence of a reasonable amount of free lime (as the result of its expansive reaction with ambient moisture). Some fluxing impurities (e.g. alkalis) present in the waste materials improve the overall reactivity of the mixture and induces the combination of the lime in CR3. Raman, XPS and FIB techniques were used to fully characterise the aged cements

Nicotine Oral Inhalation

Science.gov (United States)

... with a smoking cessation program, which may include support groups, counseling, or specific behavioral change techniques. Nicotine inhalation ... and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or ...

Radiation dose estimates and hazard evaluations for inhaled airborne radionuclides: Final report

International Nuclear Information System (INIS)

Mewhinney, J.A.

1987-09-01

The project objective was to conduct confirmatory research on physical chemical characteristics of aerosols produced during manufacture of mixed plutonium and uranium oxide nuclear fuel, to determine the radiation dose distribution in tissues of animals after inhalation exposure to representative aerosols of these materials, and to provide estimates of the relationship of radiation dose and biological response in animals after such inhalation exposure. The first chapter summarizes the physical chemical characterization of samples of aerosols collected from gloveboxes at industrial facilities during normal operations. This chapter provides insights into key aerosol characteristics which are of potential importance in determining the biological fate of specific radionuclides contained in the particulates that would be inhaled by humans following accidental release. The second chapter describes the spatial and temporal distribution of radiation dose in tissues of three species of animals exposed to representative aerosols collected from the industrial facilities. These inhalation studies provide a basis for comparison of the influence of physical chemical form of the inhaled particulates and the variability among species of animal in the radiation dose to tissue. The third chapter details to relationship between radiation dose and biological response in rats exposed to two aerosol forms each at three levels of initial pulmonary burden. This study, conducted over the lifespan of the rats and assuming results to be applicable to humans, indicates that the hazard to health due to inhalation of these industrial aerosols is not different than previously determined for laboratory produced aerosol of PuO 2 . Each chapter is processed separately for the data base

Variational formulation based analysis on growth of yield front in ...

African Journals Online (AJOL)

The present study investigates the growth of elastic-plastic front in rotating solid disks of non-uniform thickness having exponential and parabolic geometry variation. The problem is solved through an extension of a variational method in elastoplastic regime. The formulation is based on von-Mises yield criterion and linear ...

Inhalation treatment of lung cancer: the influence of composition, size and shape of nanocarriers on their lung accumulation and retention

International Nuclear Information System (INIS)

Garbuzenko, Olga B.; Mainelis, Gediminas; Taratula, Oleh; Minko, Tamara

2014-01-01

Various nanoparticles have been designed and tested in order to select optimal carriers for the inhalation delivery of anticancer drugs to the lungs. The following nanocarriers were studied: micelles, liposomes, mesoporous silica nanoparticles (MSNs), poly propyleneimine (PPI) dendrimer-siRNA complexes nanoparticles, quantum dots (QDs), and poly (ethylene glycol) polymers. All particles were characterized using the following methods: dynamic light scattering, zeta potential, atomic force microscopy, in vitro cyto- and genotoxicity. In vivo organ distribution of all nanoparticles, retention in the lungs, and anticancer effects of liposomes loaded with doxorubicin were examined in nude mice after the pulmonary or intravenous delivery. Significant differences in lung uptake were found after the inhalation delivery of lipid-based and non-lipid-based nanoparticles. The accumulation of liposomes and micelles in lungs remained relatively high even 24 h after inhalation when compared with MSNs, QDs, and PPI dendrimers. There were notable differences between nanoparticle accumulation in the lungs and other organs 1 and 3 h after inhalation or intravenous administrations, but 24 h after intravenous injection all nanoparticles were mainly accumulated in the liver, kidneys, and spleen. Inhalation delivery of doxorubicin by liposomes significantly enhanced its anticancer effect and prevented severe adverse side effects of the treatment in mice bearing the orthotopic model of lung cancer. The results of the study demonstrate that lipid-based nanocarriers had considerably higher accumulation and longer retention time in the lungs when compared with non-lipid-based carriers after the inhalation delivery. These particles are most suitable for effective inhalation treatment of lung cancer

Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

DEFF Research Database (Denmark)

Sørli, Jorid Birkelund; Huang, Yishi; Da Silva, Emilie

2018-01-01

impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if they inhibited LS function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e. the in vitro method predicted...... the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large...... numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21...

Laryngeal Trauma Following an Inhalation Injury: A Review and Case Report.

Science.gov (United States)

Hogg, Gemma; Goswamy, Jay; Khwaja, Sadie; Khwaja, Nadeem

2017-05-01

The primary concern when managing a patient with inhalation injury is security of the airway. Airflow may be impeded by both edema of the upper airway and reduction of oxygen delivery to the lower respiratory tract. Although there has been much discussion regarding management of the latter, the focus of this article is the management of the former. This review aimed to determine the optimum management in burn victims with upper airway inhalation injury as an attempt to prevent laryngeal trauma leading to long-term voice disorders and upper airway dyspnea. We describe the case of a 57-year-old woman with significant inhalation injury and discuss the natural progression of her injuries and the laryngeal controversies surrounding her care. We conclude with advice on the optimal management of this condition based on our experience, combined with current best evidence. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

A whiff of death: fatal volatile solvent inhalation abuse.

Science.gov (United States)

Steffee, C H; Davis, G J; Nicol, K K

1996-09-01

Inhalation abuse of volatile solvents, previously known generically as "glue sniffing," is typically pursued by adolescents. A wide range of legal, easily obtained products containing volatile substances are available for abuse. We report two illustrative cases of fatal volatile substance abuse: gasoline sniffing in a 20-year-old man and aerosol propellant gas inhalation (aerosol air freshener) in a 16-year-old girl with underlying reactive airway disease. Although the ratio of deaths to nonfatal inhalation escapades is extremely low, volatile solvent abuse carries the risk of sudden death due to cardiac arrest after a dysrhythmia or vasovagal event, central nervous system respiratory depression, hypoxia and hypercapnia due to the techniques of inhalation, and other mechanisms. Investigation of the patient's substance abuse history, examination of the scene of death, and special toxicologic analyses are critical to identifying volatile substance inhalation abuse as the cause of death because anatomic autopsy findings will typically be nonspecific. Above all, physicians must suspect the diagnosis of volatile substance inhalation abuse, especially in any case of sudden death involving an otherwise healthy young person.

Mutual information based CT registration of the lung at exhale and inhale breathing states using thin-plate splines

International Nuclear Information System (INIS)

Coselmon, Martha M.; Balter, James M.; McShan, Daniel L.; Kessler, Marc L.

2004-01-01

The advent of dynamic radiotherapy modeling and treatment techniques requires an infrastructure to weigh the merits of various interventions (breath holding, gating, tracking). The creation of treatment planning models that account for motion and deformation can allow the relative worth of such techniques to be evaluated. In order to develop a treatment planning model of a moving and deforming organ such as the lung, registration tools that account for deformation are required. We tested the accuracy of a mutual information based image registration tool using thin-plate splines driven by the selection of control points and iterative alignment according to a simplex algorithm. Eleven patients each had sequential CT scans at breath-held normal inhale and exhale states. The exhale right lung was segmented from CT and served as the reference model. For each patient, thirty control points were used to align the inhale CT right lung to the exhale CT right lung. Alignment accuracy (the standard deviation of the difference in the actual and predicted inhale position) was determined from locations of vascular and bronchial bifurcations, and found to be 1.7, 3.1, and 3.6 mm about the RL, AP, and IS directions. The alignment accuracy was significantly different from the amount of measured movement during breathing only in the AP and IS directions. The accuracy of alignment including thin-plate splines was more accurate than using affine transformations and the same iteration and scoring methodology. This technique shows promise for the future development of dynamic models of the lung for use in four-dimensional (4-D) treatment planning

Comparison of propofol based anaesthesia to conventional inhalational general anaesthesia for spine surgery

Directory of Open Access Journals (Sweden)

L D Mishra

2011-01-01

Full Text Available Background : Often conventional Inhalational agents are used for maintenance of anaesthesia in spine surgery. This study was undertaken to compare propofol with isoflurane anaesthesia with regard to haemodynamic stability, early emergence, postoperative nausea and vomiting (PONV and early assessment of neurological functions. Patients & Methods: Eighty ASA grade I &II adult patients were randomly allocated into two groups. Patients in study group received inj propofol for induction as well as for maintenance along with N 2O+O2 and the control group patients received inj thiopentone for induction and N 2 O+O 2 +isoflurane for maintenance. BIS monitoring was used for titrating the anaesthetic dose adjustments in all patients. All patients received fentanyl boluses for intraoperative analgesia and atracurium as muscle relaxant. Statistical data containing haemodynamic parameters, PONV, emergence time, dose of drug consumed & quality of surgical field were recorded and compared using student t′ test and Chi square test. Results: The haemodynamic stability was coparable in both the groups. The quality of surgical field were better in study group. Though there was no significant difference in the recovery profile (8.3% Vs 9.02% between both the groups, the postoperative nausea and vomiting was less in propofol group than isoflurane group (25%Vs60%. The anaesthesia cost was nearly double for propofol than isoflurane anaesthesia. Conclusion: Haemodynamic stability was comparable in both the groups. There was no significant difference in the recovery time between intravenous and inhalational group. Patients in propofol group were clear headed at awakening and were better oriented to place than inhalational group.

Advances in Nanotechnology for Efficacious and Stable Formulation Development

Science.gov (United States)

Putcha, Lakshimi

2012-01-01

Current operational medical kits aboard the International Space Station (ISS) include an array of medications intended for the treatment of minor ambulatory care symptoms, first aid, and basic life support. All medications contained in the flight kits are commercially available off-the-shelf formulations used for treatment of illnesses on Earth. However, transport and stowage of supplies including medications for space missions are exposed to adverse environmental conditions and extended shelf-life demands. Proposed missions to Mars and near-Earth objects such as asteroid 1999 AO10 will present crew health risk that is different both quantitatively and qualitatively from those encountered on ISS missions. Few drug options are available at the present time for mitigation of crew health risk of planned space exploration missions. Alternatives to standard oral formulations that include sustained and targeted delivery technologies for preventive healthcare in space will be a welcome addition to the space formulary and may include controlled release topical, sub-cutaneous, intranasal and inhalation dosage forms. An example of such a technology development endeavor can be nanotechnology-based multi-stage drug cocktail and vaccine delivery systems. Nanostructures also have the ability to protect drugs encapsulated within them from physiologic degradation, target their delivery with sustained release and are suitable for per oral routes of administration. The use of nanostructures such as polymeric nanoparticles offers a non-invasive approach for penetrating the blood brain barrier. Finally, nanotechnology offers great potential for the development of safe and efficacious drug delivery systems for preventive health care in space and on Earth.

In vitro dose comparison of Respimat® inhaler with dry powder inhalers for COPD maintenance therapy

Directory of Open Access Journals (Sweden)

Ciciliani A

2017-05-01

Full Text Available Anna-Maria Ciciliani,1,2 Peter Langguth,1 Herbert Wachtel2 1Institute of Pharmacy and Biochemistry, Faculty 09 (Chemistry, Pharmaceutics and Geosciences, Johannes Gutenberg University, Mainz, 2Analytical Development Department, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Background: Combining in vitro mouth–throat deposition measurements, cascade impactor data and computational fluid dynamics (CFD simulations, four different inhalers were compared which are indicated for chronic obstructive pulmonary disease (COPD treatment.Methods: The Respimat inhaler, the Breezhaler, the Genuair, and the Ellipta were coupled to the idealized Alberta throat model. The modeled dose to the lung (mDTL was collected downstream of the Alberta throat model using either a filter or a next generation impactor (NGI. Idealized breathing patterns from COPD patient groups – moderate and very severe COPD – were applied. Theoretical lung deposition patterns were assessed by an individual path model.Results and conclusion: For the Respimat the mDTL was found to be 59% (SD 5% for the moderate COPD breathing pattern and 67% (SD 5% for very severe COPD breathing pattern. The percentages refer to nominal dose (ND in vitro. This is in the range of 44%–63% in vivo in COPD patients who display large individual variability. Breezhaler showed a mDTL of 43% (SD 2% for moderate disease simulation and 51% (SD 2% for very severe simulation. The corresponding results for Genuair are mDTL of 32% (SD 2% for moderate and 42% (SD 1% for very severe disease. Ellipta vilanterol particles showed a mDTL of 49% (SD 3% for moderate and 55% (SD 2% for very severe disease simulation, and Ellipta fluticasone particles showed a mDTL of 33% (SD 3% and 41% (SD 2%, respectively for the two breathing patterns. Based on the throat output and average flows of the different inhalers, CFD simulations were performed. Laminar and turbulent steady flow calculations indicated that

Inhaled antibiotics in non-cystic fibrosis bronchiectasis: A meta-analysis.

Science.gov (United States)

Xu, Li; Zhang, Fei; Du, Shuai; Yu, Qi; Chen, Lin; Long, Li-Hui; Li, Ya-Ming; Jia, Ai-Hua

2016-09-01

To evaluate the efficacy and safety of inhaled antibiotics for the treatment of non-cystic fibrosis bronchiectasis (NCFB). Pubmed, Cochrane library, Embase, Elsevier, OVID, Springerlink, Web of knowledge and NEJM were searched for randomized controlled trials (RCTs) on inhaled antibiotics in treatment of NCFB from inception until April 2015. Meta-analysis was conducted to assess the efficacy and safety of inhaled antibiotics in the treatment of NCFB. Twelve RCTs involving 1154 participants were included. They showed that inhaled antibiotics were more effective in reduction of sputum bacterial density, eradication of P. aeruginosa, prolonged time to exacerbation and reduction of new pathogens emergence with no significant difference in adverse events compared with control groups. However, we did not find significant benefits of inhaled antibiotics in reducing the risk of acute exacerbation, improving health-related quality of life and reduction of P. aeruginosa resistance. Moreover, inhaled antibiotics exerted a statistically significant reduction in FEV1%. Inhaled antibiotics may be an alternative pathway to inhibit airway inflammation with no more adverse events in patients with NCFB.

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

Science.gov (United States)

Westerik, Janine A. M.; Carter, Victoria; Chrystyn, Henry; Burden, Anne; Thompson, Samantha L.; Ryan, Dermot; Gruffydd-Jones, Kevin; Haughney, John; Roche, Nicolas; Lavorini, Federico; Papi, Alberto; Infantino, Antonio; Roman-Rodriguez, Miguel; Bosnic-Anticevich, Sinthia; Lisspers, Karin; Ställberg, Björn; Henrichsen, Svein Høegh; van der Molen, Thys; Hutton, Catherine; Price, David B.

2016-01-01

Abstract Objective: Correct inhaler technique is central to effective delivery of asthma therapy. The study aim was to identify factors associated with serious inhaler technique errors and their prevalence among primary care patients with asthma using the Diskus dry powder inhaler (DPI). Methods: This was a historical, multinational, cross-sectional study (2011–2013) using the iHARP database, an international initiative that includes patient- and healthcare provider-reported questionnaires from eight countries. Patients with asthma were observed for serious inhaler errors by trained healthcare providers as predefined by the iHARP steering committee. Multivariable logistic regression, stepwise reduced, was used to identify clinical characteristics and asthma-related outcomes associated with ≥1 serious errors. Results: Of 3681 patients with asthma, 623 (17%) were using a Diskus (mean [SD] age, 51 [14]; 61% women). A total of 341 (55%) patients made ≥1 serious errors. The most common errors were the failure to exhale before inhalation, insufficient breath-hold at the end of inhalation, and inhalation that was not forceful from the start. Factors significantly associated with ≥1 serious errors included asthma-related hospitalization the previous year (odds ratio [OR] 2.07; 95% confidence interval [CI], 1.26–3.40); obesity (OR 1.75; 1.17–2.63); poor asthma control the previous 4 weeks (OR 1.57; 1.04–2.36); female sex (OR 1.51; 1.08–2.10); and no inhaler technique review during the previous year (OR 1.45; 1.04–2.02). Conclusions: Patients with evidence of poor asthma control should be targeted for a review of their inhaler technique even when using a device thought to have a low error rate. PMID:26810934

Evaluation of alternative Plutella xylostella control by two Isaria fumosorosea conidial formulations - oil-based formulation and wettable powder - combined with Bacillus thuringiensis.

Science.gov (United States)

Nian, Xiao-Ge; He, Yu-Rong; Lu, Li-Hua; Zhao, Rui

2015-12-01

Entomopathogenic fungi are potential candidates for controlling the diamondback moth Plutella xylostella (L.) (Lepidoptera: Plutellidae). The control efficacy of two Isaria fumosorosea conidial formulations - wettable powder and oil-based formulation - combined with Bacillus thuringiensis against P. xylostella was tested. In the laboratory, the combined application of two pathogens increased larval mortality either in an additive or a synergistic way. P. xylostella larvae treated with oil-based formulation died sooner than larvae infected with wettable powder. For pot and field experiments, each formulation was applied alone or combined with B. thuringiensis 668 µg mL(-1) , and then larval mortality, pupation rate, adult emergence rate, female longevity and fecundity were recorded. In pot experiments there was no evidence of any antagonistic effects between the two pathogens. Combined application of B. thuringiensis and a high concentration of the two I. fumosorosea formulations resulted in higher mortality (84.4 and 86.2%) with minimum pupation (15.6 and 11.9%) and adult emergence rates (8.7 and 7.0%). Female longevity and fecundity were significantly reduced by the two formulations at high concentration compared with the control. Similar results were also observed in field experiments. The combined application of I. fumosorosea and B. thuringiensis is a promising alternative strategy for P. xylostella control. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Modeling the effect of continuous infusion DTPA therapy on the retention and dosimetry of inhaled actinides

International Nuclear Information System (INIS)

Guilmette, R.A.; Muggenburg, B.A.

1988-01-01

A biokinetic model of the treatment of dogs that inhaled 241 AmO 2 aerosols with continuously infused DTPA has been adapted from a model previously published by Mewhinney and Griffith. This model simulated both the tissue retention and excretion of 241 Am, and was used to estimate the cumulative radiation doses to tissues at risk from 241 Am alpha radiation. The results showed that at 64 days after exposure, the liver dose of the DTPA-treated animals was 3% that of the corresponding controls, the skeletal dose was 2%, the kidney dose was 4%, and the lung dose was 67% of controls. This paper describes a biokinetic and dosimetric model that was adapted from a previously published model. It was developed to provide a means of estimating radiation doses for cases where continuously infused DTPA therapy is used to reduce radiation dose. The model was formulated for the case of 241 Am0 2 inhalation, a physicochemical form of Am that is moderately soluble in vivo, and one to which people have been exposed. Because adequate human data, particularly tissue data, are not available from cases of accidental human exposure to 241 Am, two published data sets from experiments in which Beagle dogs inhaled 241 Am0 2 aerosols have been used to obtain parameter estimates for the model. The model simulations were then used to provide dose estimates with and without infused-DTPA therapy. (author)

Clinical effectiveness of the Respimat® inhaler device in managing chronic obstructive pulmonary disease: evidence when compared with other handheld inhaler devices

Directory of Open Access Journals (Sweden)

et al

2011-02-01

Full Text Available Felix SF Ram1, Celso R Carvallho2, John White31School of Health and Social Services, Massey University, Auckland, New Zealand; 2Department of Physical Therapy, School of Medicine, University of São Paulo, Brazil; 3York Hospitals NHS Foundation Trust, York Hospital, York, UKObjectives: Medication for the management of chronic obstructive pulmonary disease (COPD may be delivered by a number of different inhaler devices. This study was undertaken to determine the clinical effectiveness of the Respimat® handheld inhaler device compared with other handheld inhaler devices for the delivery of medication in stable COPD.Methodology: A systematic review of high-quality randomized controlled clinical trials comparing Respimat with other inhaler devices using the same medication was performed. Studies were searched for in the Cochrane Central Register of Controlled Trials as well as other relevant electronic databases. Manufacturers of inhaled COPD medication were also contacted for potential trials.Results: Seven studies of high methodological quality with 3813 participants were included in the review. Three trials used Handihaler® as the comparator inhaler, three used a chlorofluorocarbon metered-dose inhaler (CFC-MDI, and one trial used a hydroflouroalkane (HFA-MDI. When Respimat was compared with Handihaler, the following reported outcomes were not significantly different: trough forced expiratory volume in 1 second (FEV1 (weighted mean difference [WMD] 0.01 L; P = 0.14, trough forced vital capacity (FVC (WMD 0.001 L: P = 0.88, peak FEV1 (WMD 0.01 L: P = 0.08, peak FVC (WMD 0.01 L: P = 0.55, morning peak expiratory flow rate (PEFR (WMD 5.06 L/min: P = 0.08, and evening PEFR (WMD 4.39 L/min: P = 0.15. Furthermore, there were no differences when Respimat was compared with Handihaler for risk of exacerbations (relative risk [RR] 0.94: P = 0.81, dry mouth (RR 1.57: P = 0.34, or nasopharyngitis (RR 1.42: P = 0.22. For Respimat compared with CFC-MDI, the

Inhaling habits among smokers of different types of cigarette

Energy Technology Data Exchange (ETDEWEB)

Wald, N.J.; Idle, M.; Boreham, J.; Bailey, A.

1980-12-01

Inhaling habits were studied in 1316 men who freely smoked their usual brands of cigarette. An index of inhaling was calculated for each person by dividing the estimated increase in carboxyhaemoglobin level from a standard number of cigarettes by the carbon monoxide yield of the cigarette smoked. Smokers of ventilated filter cigarettes inhaled 82% more than smokers of plain cigarettes (p less than 0.001) and those who smoked unventilated filter cigarettes inhaled 36% more (p less than 0.001). Cigarette consumption was similar among smokers of each type of cigarette. Assuming that the intake of tar and nicotine is proportional to the inhaling index, the intake in either group of filter cigarette smokers would have been less than that in plain cigarette smokers. Among smokers of unventilated cigarettes, however, the intake would not have been much less.

Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels

Directory of Open Access Journals (Sweden)

Nicolas Defarge

2016-02-01

Full Text Available Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH, the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18–2000 times for co-formulants, 8–141 times for formulations, and not the declared active ingredient glyphosate (G alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

Opportunities for inhaler device selection in elderly patients with asthma or COPD

Directory of Open Access Journals (Sweden)

Barrons R

2015-12-01

Full Text Available Robert Barrons,1 James Wheeler,2 J Andrew Woods1 1Wingate University School of Pharmacy, Wingate, NC, USA; 2University of Tennessee Health Science Center, Nashville, TN, USA Abstract: An anticipated surge in the elderly population will be accompanied by a rise in aging patients with asthma or COPD. Clinician selection of inhalers needs to address the unique challenges to elderly patients. These challenges to the use of inhalers include diminished physical and cognitive abilities, as well as cost reimbursement issues associated with polypharmacy and the Medicare gap. Clinicians should consider patient preferences for an inhaler device that provides ease of administration, and addresses conveniences such as portability, visual, and auditory indicators of dosing completion. The addition of spacer devices resolves hand-breath coordination difficulty with pressurized metered dose inhalers, but reduces overall inhaler convenience. Soft mist inhalers (Respimat® improve ease of administration, but use may be limited by cost and formulary availability. Multiple dose dry powder inhalers provide convenience and simplified use by requiring only one to two steps prior to administration, but concerns of peak inspiratory flow requirements remain among patients with advanced age and severity of COPD. If unaddressed, these challenges to inhaler selection contribute to inappropriate use of inhalers in 41% to 69% of patients, accompanied by at least 51% non-adherence to treatment. Clinicians must first avail themselves of reputable educational resources regarding new inhaler developments and administration, for competent patient instruction. Patient education should include a checklist of inhaler technique, with physical demonstration of each device by the patient and provider. Device demonstration significantly improves inhaler technique and identifies the need for nebulization therapy. Clinician and patient knowledge of available inhalers and their

Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin.

Science.gov (United States)

Andrade, Fernanda; das Neves, José; Gener, Petra; Schwartz, Simó; Ferreira, Domingos; Oliva, Mireia; Sarmento, Bruno

2015-10-01

Pulmonary delivery of drugs for both local and systemic action has gained new attention over the last decades. In this work, different amphiphilic polymers (Soluplus®, Pluronic® F68, Pluronic® F108 and Pluronic® F127) were used to produce lyophilized formulations for inhalation of insulin. Development of stimuli-responsive, namely glucose-sensitive, formulations was also attempted with the addition of phenylboronic acid (PBA). Despite influencing the in vitro release of insulin from micelles, PBA did not confer glucose-sensitive properties to formulations. Lyophilized powders with aerodynamic diameter (<6 μm) compatible with good deposition in the lungs did not present significant in vitro toxicity for respiratory cell lines. Additionally, some formulations, in particular Pluronic® F127-based formulations, enhanced the permeation of insulin through pulmonary epithelial models and underwent minimal internalization by macrophages in vitro. Overall, formulations based on polymeric micelles presenting promising characteristics were developed for the delivery of insulin by inhalation. The ability to deliver other systemic drugs via inhalation has received renewed interests in the clinical setting. This is especially true for drugs which usually require injections for delivery, like insulin. In this article, the authors investigated their previously developed amphiphilic polymers for inhalation of insulin in an in vitro model. The results should provide basis for future in vivo studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Inhalant abuse of computer cleaner manifested as angioedema.

Science.gov (United States)

Kurniali, Peter C; Henry, Letitia; Kurl, Rita; Meharg, Joseph V

2012-01-01

Inhalant abuse is the intentional inhalation of chemical vapors or volatile substance to achieve a euphoric effect. Although no statistical data are reported yet, inhalant abuse is potentially life-threatening and has resulted in a wide range of toxic effects such as central nervous system depression, seizures, aspiration, cardiac arrhythmia, asphyxiation, hypoxia, metabolic acidosis, and sudden death among others. We are reporting a 25-year-old white man who was brought to the emergency department after inhaling aerosolized computer-cleaning spray composed of difluoroethane. He was found to have marked upper and lower lip facial swelling consistent with angioedema. The patient also had a prolonged QT interval, mild inspiratory stridor, but no urticaria. In this case, we believe the difluoroethane-related angioedema represents either idiopathic or bradykinin-induced angioedema.

Inhaled plutonium nitrate in dogs

International Nuclear Information System (INIS)

Dagle, G.E.

1987-01-01

The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. They have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 3 tables

Inhaled plutonium nitrate in dogs

International Nuclear Information System (INIS)

Dagle, G.E.

1986-01-01

The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. The authors have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 4 tables

Inhaled plutonium nitrate in dogs

International Nuclear Information System (INIS)

Dagle, G.E.

1982-01-01

The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in the prediction of health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; as described in previous Annual Reports, lymphopenia and neutropenia occurred at the two highest dose levels. Radiation pneumonitis, lung cancer, and bone cancer have been observed at the highest dose levels

Efficacy of tooth whitening with different calcium phosphate-based formulations.

Science.gov (United States)

Jin, Jian; Xu, Xiaohui; Lai, Guangyun; Kunzelmann, Karl-Heinz

2013-08-01

The aim of this in-vitro study was to evaluate the efficacy of tooth whitening using different calcium phosphate-based formulations. Teeth were treated with three different hydroxyapatite preparations at different concentrations and with two control preparations; each tooth was treated a total of three times. After application of the last material, hydrodynamic shear force was applied to mimic mechanical loading. After each treatment, tooth color was measured using a dental spectrophotometer, and the mean changes in L*a*b* values between different measurements were expressed as ∆E. The results indicated significant differences between the materials, but neither dose- nor time-dependent associations were found. The suspension containing tricalcium phosphate (10 wt%) showed the most obvious color change (∆E = 2.20 ± 0.90), while the suspension containing zinc-carbonate-apatite (20 wt%) showed the least obvious color change (∆E = 0.91 ± 0.50). Calcium phosphate-based formulations that can adhere to the enamel surface and contribute to tooth whitening have promising tooth-whitening potential. © 2013 Eur J Oral Sci.

Formulation de microparticules et de gelules a base de Sida acuta ...

African Journals Online (AJOL)

Formulation de microparticules et de gelules a base de Sida acuta (Malvaceae) par spray drying. A N'guessan, A.A. Koffi, L.I. Dally, K Issoufou, S Any-Grah-Aka, J.A. Lia, A Kouassi-Tuo, K.C. N'guessan-Gnaman ...

Phyto-inhalation for treatment of complications of acute respiratory viral diseases

Directory of Open Access Journals (Sweden)

I.B. Ershova

2017-03-01

Full Text Available Inhalations (inhalation of medicinal substances are one of the effective ways to treat upper respiratory tract diseases and colds. Inhalation therapy is used to treat rhinitis, sinusitis, tonsillitis, pharyngitis, laryngitis, bronchitis and pneumonia, which can be complications of acute respiratory viral infections. The main rules of inhalation are as follows to conduct the procedure better after 1.5 hours after eating; clothes should not impede breathing; the procedure can be carried out only while sitting or standing; solution for the inhaler for treatment of bronchitis should be fresh; it is necessary to strictly keep the prescribed dosage; the time of the procedure should also be respected — usually it is from 1 to 4 minutes, sometimes for adults up to 10 minutes, for children the inhalation period is shorter — 1–2 minutes. Contraindications to inhalation are body temperature above 37.5 degrees; propensity to nasal blee­ding in a patient; propensity to increased arterial pressure, with cardiovascular failure; purulent inflammation of the tonsils; respiratory failure. The procedure should be stopped immediately in case of appearance of adverse symptoms such as shortness of breath, dizziness, difficulty in breathing. Therefore, inhalations must be prescribed by a doctor after examination of a patient. During inhalations in rhinitis, you should try to inhale the vapor through the nose. For effective treatment of rhinitis, inhalations from conife­rous plants are very suitable: fir, pine, juniper, larch, from steamed dried chamomile flowers, mint, and blackberry leaves. Honey inhalations can be used for the treatment of acute and chronic diseases of the upper respiratory tract (tonsillitis, pharyngitis, laryngitis and tracheitis. Medical herbal inhalation for children should be carried out from the age of two years. This must be done under the constant supervision of an adult. Leaves of coniferous trees: pine, fir, if or juniper, cedar

Does inhalation injury predict mortality in burns patients or require redefinition?

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Youngmin Kim

Full Text Available Inhalation injury is known to be an important factor in predicting mortality in burns patients. However, the diagnosis is complicated by the heterogeneous presentation and inability to determine the severity of inhalation injury. The purpose of this study was to identify clinical features of inhalation injury that affect mortality and the values that could predict the outcome more precisely in burns patients with inhalation injury. This retrospective observational study included 676 burns patients who were over 18 years of age and hospitalized in the Burns Intensive Care Unit between January 2012 and December 2015. We analyzed variables that are already known to be prognostic factors (age, percentage of total body surface area (%TBSA burned, and inhalation injury and factors associated with inhalation injury (carboxyhemoglobin and PaO2/FiO2 [PF] ratio by univariate and multivariate logistic regression. Age group (odds ratio [OR] 1.069, p<0.001, %TBSA burned (OR 1.100, p<0.001, and mechanical ventilation (OR 3.774, p<0.001 were identified to be significant predictive factors. The findings for presence of inhalation injury, PF ratio, and carboxyhemoglobin were not statistically significant in multivariate logistic regression. Being in the upper inhalation group, the lower inhalation group, and having a PF ratio <100 were identified to be significant predictors only in univariate logistic regression analysis (OR 4.438, p<0.001; OR 2.379, p<0.001; and OR 2.765, p<0.001, respectively. History and physical findings are not appropriate for diagnosis of inhalation injury and do not predict mortality. Mechanical ventilation should be recognized as a risk factor for mortality in burns patients with inhalation injury.

Special aspects of pharmacokinetics of inhalation anesthesia.

Science.gov (United States)

Hendrickx, J F A; De Wolf, A

2008-01-01

(D) adjustments have to be made, while with a low FGF F(D) has to be adjusted according to a pattern that follows the decreasing uptake pattern in the body. The ability to model and predict the uptake pattern of the individual patient and the resulting kinetics in a circle system could therefore help guide the anesthesiologist in the use of low-flow anesthesia with conventional anesthesia machines. Several authors have developed model-based low FGF administration schedules, but biologic variability limits the performance of any model, and therefore end-expired gas analysis is obligatory. Because some fine-tuning based on end-expired gas analysis will always be needed, some clinicians may not be inclined to use very low FGF in a busy operating room, considering the perceived increase in complexity. This practice may be facilitated by the development of anesthesia machines that use closed circuit anesthesia (CCA) with end-expired feedback control--they "black box" these issues (see Chapter 21). In this chapter, we first explore how and why the kinetic properties of intravenous and inhaled anesthetics have been modeled differently. Next, we will review the method most commonly used to describe the kinetics of inhaled agents, the F(A)/F(I) vs time curve that describes how the alveolar (F(A)) approaches the inspired (F(I)) fraction (in the gas phase, either "fraction," "concentration," or "partial pressure" can be used). Finally, we will reintroduce the concept of the general anesthetic equation to explain why the use of low-flow or closed circuit anesthesia has rekindled interest in the modeling of pharmacokinetics of inhaled anesthetics. Clinical applications of some of these models are reviewed. A basic understanding of the circle system is required, and will be provided in the introduction.

Knowledge of spacer device, peak flow meter and inhaler technique ...

African Journals Online (AJOL)

Background: Metered dose inhalers are cornerstone in effective management of bronchial asthma when correctly used. Most studies hitherto have focused on assessing patient's knowledge of inhaler technique. We sought to assess the knowledge of inhaler technique, spacer device and peak flow meter among doctors and ...

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 4: proposing a new lipid formulation performance classification system.

Science.gov (United States)

Williams, Hywel D; Sassene, Philip; Kleberg, Karen; Calderone, Marilyn; Igonin, Annabel; Jule, Eduardo; Vertommen, Jan; Blundell, Ross; Benameur, Hassan; Müllertz, Anette; Porter, Christopher J H; Pouton, Colin W

2014-08-01

The Lipid Formulation Classification System Consortium looks to develop standardized in vitro tests and to generate much-needed performance criteria for lipid-based formulations (LBFs). This article highlights the value of performing a second, more stressful digestion test to identify LBFs near a performance threshold and to facilitate lead formulation selection in instances where several LBF prototypes perform adequately under standard digestion conditions (but where further discrimination is necessary). Stressed digestion tests can be designed based on an understanding of the factors that affect LBF performance, including the degree of supersaturation generated on dispersion/digestion. Stresses evaluated included decreasing LBF concentration (↓LBF), increasing bile salt, and decreasing pH. Their capacity to stress LBFs was dependent on LBF composition and drug type: ↓LBF was a stressor to medium-chain glyceride-rich LBFs, but not more hydrophilic surfactant-rich LBFs, whereas decreasing pH stressed tolfenamic acid LBFs, but not fenofibrate LBFs. Lastly, a new Performance Classification System, that is, LBF composition independent, is proposed to promote standardized LBF comparisons, encourage robust LBF development, and facilitate dialogue with the regulatory authorities. This classification system is based on the concept that performance evaluations across three in vitro tests, designed to subject a LBF to progressively more challenging conditions, will enable effective LBF discrimination and performance grading. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Inhaled plutonium oxide in dogs

International Nuclear Information System (INIS)

Park, J.F.

1985-01-01

This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols to obtain graded levels of initial lung burdens are being observed for lifespan dose-effect relationships. Mortality due to radiation pneumonitis and lung tumor increased in the four highest dose-level groups exposed to 239 PuO 2 , during the 13-yr postexposure period. During the 10 1/2 years after exposure to 238 PuO 2 , mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 year after exposure, was the earliest observed effect after inhalation of either 239 PuO 2 or 238 PuO 2 in the four highest dose-level groups that had initial lung burdens greater than or equal to 80 nCi. 3 figures, 6 tables

Terbutaline accumulates in blood and urine following daily therapeutic inhalation

DEFF Research Database (Denmark)

Krogh, Nanna; Rzeppa, Sebastian; Dyreborg, Anders

2017-01-01

×d) of inhaled terbutaline. After inhalation of terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of terbutaline. Samples were analyzed by high...

Effect of inhaled formoterol and budesonide on exacerbations of asthma

NARCIS (Netherlands)

Pauwels, RA; Lofdahl, CG; Postma, DS; Tattersfield, AE; OByrne, P; Barnes, PJ; Ullman, A

1997-01-01

Background The role of long-acting, inhaled beta(2)-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. Methods After a four-week run-in period of treatment

Treatment of proctalgia fugax with salbutamol inhalation.

Science.gov (United States)

Eckardt, V F; Dodt, O; Kanzler, G; Bernhard, G

1996-04-01

Although no generally effective treatment for proctalgia fugax is known, inhalation of salbutamol has been reported to shorten pain attacks in isolated cases. We conducted a randomized, double-blind, placebo-controlled, crossover trial of inhaled salbutamol in 18 patients with proctalgia fugax. The clinical effect was evaluated by recording the duration of severe pain and discomfort during acute attacks. In addition, anorectal motility recordings were analyzed for possible changes in anal resting tone, sphincter relaxation during rectal distension and in rectal compliance prior to and following administration of the two test substances. Sixteen patients completed all investigations. Compared to placebo, salbutamol inhalation shortened the duration of severe pain (p = 0.019). The effect was most marked in patients having prolonged attacks. In the asymptomatic state, neither salbutamol nor placebo led to a significant change in anal resting pressure, anal relaxation during rectal distension, or rectal compliance. Salbutamol also did not alter the threshold for rectal sensation. Salbutamol inhalation shortens attacks of severe pain in patients with proctalgia fugax. The mechanism of this effect remains unexplained.

Inhalation Exposure Input Parameters for the Biosphere Model

Energy Technology Data Exchange (ETDEWEB)

M. Wasiolek

2006-06-05

This analysis is one of the technical reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), referred to in this report as the biosphere model. ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. ''Inhalation Exposure Input Parameters for the Biosphere Model'' is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the biosphere model is presented in Figure 1-1 (based on BSC 2006 [DIRS 176938]). This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and how this analysis report contributes to biosphere modeling. This analysis report defines and justifies values of atmospheric mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of the biosphere model to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception. This

Inhalation Exposure Input Parameters for the Biosphere Model

International Nuclear Information System (INIS)

M. Wasiolek

2006-01-01

This analysis is one of the technical reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), referred to in this report as the biosphere model. ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. ''Inhalation Exposure Input Parameters for the Biosphere Model'' is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the biosphere model is presented in Figure 1-1 (based on BSC 2006 [DIRS 176938]). This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and how this analysis report contributes to biosphere modeling. This analysis report defines and justifies values of atmospheric mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of the biosphere model to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception. This report is concerned primarily with the

Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

Science.gov (United States)

Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

2013-02-01

Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

Topical gel formulation and stability assessment of platelet lysate based on turbidimetric method

Directory of Open Access Journals (Sweden)

Soliman Mohammadi Samani

2015-06-01

Full Text Available Platelet-rich growth factors have attracted attentions of scientists and clinical practitioners who are involved in wound healing and regenerative medicine extensively, according to their unprecedented potential of promoting and catalyzing healing process. Platelet-rich growth factors are cost-benefit, available and more stable than recombinant human growth factors. These appealing characteristics have converted PRGF to one of the popular candidates for treatment of variety of wounds. According to these valuable properties, we decided to formulate and assess the effect of different excipients on the stability of such valuable protein based formulations. Different excipients have been chosen according to their effective ness on the stability of proteins and their application in other similar formulations. The stabilizing effect of excipients was evaluated by measuring heat-induced aggregation of growth factors by turbidimetric assay. Glycerol, glycine and dextrose were chosen as stabilizing excipients for these formulations. The results show that dextrose has more stabilizing effect on prevention of heat induced aggregation of the platelet lysate growth factors than glycerol and glycine. All of the formulations also contained antioxidant, chelating agents, preservative and carbopol934 in order to form appropriate gel.

The effect of smoking status on burn inhalation injury mortality.

Science.gov (United States)

Knowlin, Laquanda; Stanford, Lindsay; Cairns, Bruce; Charles, Anthony

2017-05-01

Three factors that effect burn mortality are age, total body surface of burn (TBSA), and inhalation injury. Of the three, inhalation injury is the strongest predictor of mortality thus its inclusion in the revised Baux score (age+TBSA+17* (inhalation injury, 1=yes, 0=no)). However, the weighted contribution of specific comorbidities such as smoker status on mortality has traditionally not been accounted for nor studied in this subset of burn patients. We therefore sought to examine the impact of current tobacco and/or marijuana smoking in patients with inhalation injury. A retrospective analysis of patients admitted to a regional burn center from 2002 to 2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, and smoker status. Bivariate analysis was performed and logistic regression modeling using significant variables was utilized to estimate odds of mortality. There were a total of 7640 patients over the study period. 7% (n=580) of the burn cohort with inhalation injury were included in this study. In-hospital burn mortality for inhalation injury patients was 23%. Current smokers (20%) included cigarette smokers and marijuana users, 19% and 3%, respectively. Preexisting respiratory disease (17%) was present in 36% of smokers compared to 13% of non-smokers (psmoke inhalation injury. Future prospective studies in human and/or animal models are needed to confirm these findings. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Inhaled therapy for the management of perioperative pulmonary hypertension

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C A Thunberg

2015-01-01

Full Text Available Patients with pulmonary hypertension (PH are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP. Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary-specific vasodilator, nitric oxide (NO, has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil, NO-donating drugs (sodium nitroprusside, nitroglycerin, and nitrite, and phosphodiesterase inhibitors (milrinone, sildenafil may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators.

‘Great ease and simplicity of action’: Dr Nelson’s Inhaler and the origins of modern inhalation therapy

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Barry Murnane

2017-11-01

Full Text Available Unveiled at the conclusion of a meeting of the Royal Medical and Chirurgical Society in 1861,[1] ‘Dr Nelson’s Improved Inhaler’ was one of the most important milestones in the genesis of reliable treatment of respiratory ailments in the modern era. Affordable and suitable for self-medication, the Dr Nelson’s Inhaler offered simple and reliable relief for patients with respiratory and pulmonary ailments. Conspicuous for its modesty and simplicity, it was one of the most widely produced, reproduced, and used inhalation devices in the final third of the nineteenth century. By reconstructing the ‘biography’ of the Nelson Inhaler, this article will attempt to sketch a network of medical and commercial interests and expertise in London which aligned in the 1860s to help establish inhalation as a popular, inexpensive, and trusted form of medical therapy for pulmonary ailments. This article will look at what connects physicians, apothecaries, and patients in the era: the medicines and technologies that were prescribed, made, bought, and which caused wellness, side-effects, and even death. This approach allows us to develop a narrative of respiratory illness as it was experienced by practitioners and patients alike.

A physiologically based toxicokinetic model for inhaled ethylene and ethylene oxide in mouse, rat, and human.

Science.gov (United States)

Filser, Johannes Georg; Klein, Dominik

2018-04-01

Ethylene (ET) is the largest volume organic chemical. Mammals metabolize the olefin to ethylene oxide (EO), another important industrial chemical. The epoxide alkylates macromolecules and has mutagenic and carcinogenic properties. In order to estimate the EO burden in mice, rats, and humans resulting from inhalation exposure to gaseous ET or EO, a physiological toxicokinetic model was developed. It consists of the compartments lung, richly perfused tissues, kidneys, muscle, fat, arterial blood, venous blood, and liver containing the sub-compartment endoplasmic reticulum. Modeled ET metabolism is mediated by hepatic cytochrome P450 2E1, EO metabolism by hepatic microsomal epoxide hydrolase or cytosolic glutathione S-transferase in various tissues. EO is also spontaneously hydrolyzed or conjugated with glutathione. The model was validated on experimental data collected in mice, rats, and humans. Modeled were uptake by inhalation, wash-in-wash-out effect in the upper respiratory airways, distribution into tissues and organs, elimination via exhalation and metabolism, and formation of 2-hydroxyethyl adducts with hemoglobin and DNA. Simulated concentration-time courses of ET or EO in inhaled (gas uptake studies) or exhaled air, and of EO in blood during exposures to ET or EO agreed excellently with measured data. Predicted levels of adducts with DNA and hemoglobin, induced by ET or EO, agreed with reported levels. Exposures to 10000 ppm ET were predicted to induce the same adduct levels as EO exposures to 3.95 (mice), 5.67 (rats), or 0.313 ppm (humans). The model is concluded to be applicable for assessing health risks from inhalation exposure to ET or EO. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Practice makes perfect: self-reported adherence a positive marker of inhaler technique maintenance.

Science.gov (United States)

Azzi, Elizabeth; Srour, Pamela; Armour, Carol; Rand, Cynthia; Bosnic-Anticevich, Sinthia

2017-04-24

Poor inhaler technique and non-adherence to treatment are major problems in the management of asthma. Patients can be taught how to achieve good inhaler technique, however maintenance remains problematic, with 50% of patients unable to demonstrate correct technique. The aim of this study was to determine the clinical, patient-related and/or device-related factors that predict inhaler technique maintenance. Data from a quality-controlled longitudinal community care dataset was utilized. 238 patients using preventer medications where included. Data consisted of patient demographics, clinical data, medication-related factors and patient-reported outcomes. Mixed effects logistic regression was used to identify predictors of inhaler technique maintenance at 1 month. The variables found to be independently associated with inhaler technique maintenance using logistic regression (Χ 2 (3,n = 238) = 33.24, p < 0.000) were inhaler technique at Visit 1 (OR 7.1), device type (metered dose inhaler and dry powder inhalers) (OR 2.2) and self-reported adherent behavior in the prior 7 days (OR 1.3). This research is the first to unequivocally establish a predictive relationship between inhaler technique maintenance and actual patient adherence, reinforcing the notion that inhaler technique maintenance is more than just a physical skill. Inhaler technique maintenance has an underlying behavioral component, which future studies need to investigate. BEHAVIORAL ELEMENT TO CORRECT LONG-TERM INHALER TECHNIQUES: Patients who consciously make an effort to perfect asthma inhaler technique will maintain their skills long-term. Elizabeth Azzi at the University of Sydney, Australia, and co-workers further add evidence that there is a strong behavioral component to patients retaining correct inhaler technique over time. Poor inhaler technique can limit asthma control, affecting quality of life and increasing the chances of severe exacerbations. Azzi's team followed 238 patients to

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

Science.gov (United States)

Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

2018-03-08

Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma

High Resolution Mass Spectrometry of Polyfluorinated Polyether-Based Formulation

DEFF Research Database (Denmark)

Dimzon, Ian Ken; Trier, Xenia; Frömel, Tobias

2016-01-01

High resolution mass spectrometry (HRMS) was successfully applied to elucidate the structure of a polyfluorinated polyether (PFPE)-based formulation. The mass spectrum generated from direct injection into the MS was examined by identifying the different repeating units manually and with the aid o......-fluorinated polymers. The information from MS is essential in studying the physico-chemical properties of PFPEs and can help in assessing the risks they pose to the environment and to human health. Graphical Abstract ᅟ....

Fate of inhaled azodicarbonamide in rats

International Nuclear Information System (INIS)

Mewhinney, J.A.; Ayres, P.H.; Bechtold, W.E.; Dutcher, J.S.; Cheng, Y.S.; Bond, J.A.; Medinsky, M.A.; Henderson, R.F.; Birnbaum, L.S.

1987-01-01

Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation to ADA to achieve body burdens of 24 or 1230 micrograms showed no significant differences in modes or rates of excretion of [ 14 C]ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only 14 C-labeled compound present in excreta. [ 14 C]ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for [ 14 C]ADA equivalents were not observed. The rate of buildup of [ 14 C]ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 micrograms ADA/liter. In a study extending 102 days after exposure, retention of [ 14 C]ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine

Inhaled Antibiotics in the Treatment of Nosocomial Pneumonia

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A. N. Kuzovlev

2013-01-01

Full Text Available Nosocomial pneumonia is the most common nosocomial infection in intensive care units. Rational antibiotic therapy is the basis for the treatment of nosocomial pneumonia. There is currently a challenge of the pathogens of nosocomial pneumonia being resistant to most of the antibiotics recommended for its treatment. Inhaled antibiotics used in combination with systemic drugs are an effective and safe treatment for nosocomial pneumonia. This review of literature characterizes the current possibilities of inhaled antibiotic therapy for nosocomial pneumonia in detail and describes medicaments and the advantages and disadvantages of this treatment option. Despite insufficient evidence in circumstances where the microorganisms are polyresistant and where the design of novel antibiotics shows no promise, the use of inhaled antibiotics is an important alternative in the treatment of severe nosocomial pneumonia caused by polyresistant gram-negative bacteria. Key words: nosocomial pneumonia, antibiotic therapy, inhaled antibiotics, resistance.

Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

Science.gov (United States)

Jonkman, Kelly; Duma, Andreas; Olofsen, Erik; Henthorn, Thomas; van Velzen, Monique; Mooren, René; Siebers, Liesbeth; van den Beukel, Jojanneke; Aarts, Leon; Niesters, Marieke; Dahan, Albert

2017-10-01

Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.

Inhaled Surfactant Therapy in Newborns in Artificial Lung Ventilation

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S. A. Perepelitsa

2014-01-01

Full Text Available Objective: to evaluate the efficiency of inhaled surfactant therapy in neonatal infants with respiratory failure.Subjects and methods. The trial enrolled 13 premature neonatal infants; their mean gestational age was 31.8±2.8 weeks and the birth weight was 1825±600.9 g. They had a oneminute Apgar score of 4.3±1.4. All the neonates needed mechanical ventilation (MV atbirth because the leading clinical sign was respiratory failure caused by acute intranatal hypoxia, neonatal amniotic fluid aspiration, respiratory distress syndrome (RDS, and cerebral ischemia. Curosurf was injected in a dose of 174.7±21 mg/kg in the infants with neonatal RDS at 35 minutes of life. All the babies included in the study were noted to have severe disease and prolonged MV. After stabilization of their status, the neonates received combination therapy involving surfactantBL inhalation to reduce the duration of MV. The dose of the agent was 75 mg. Results. After surfactantBL inhalation, effective spontaneous respiration occurred in 69.2% of the newborn infants; successful extubation was carried out. The median duration ofMV after surfactant BL inhalation was 22 hours (4—68 hours. There were no reintubated cases after inhalation therapy. Following surfactantBL inhalation, 4 (30.8% patients remained to be on MV as a control regimen; 3 of them had highfre quency MV. SurfactantBL inhalation made it possible to change the respiratory support regimen and to reduce MV parame ters in these babies. 

Pharmacoeconomics of inhaled anesthetic agents: considerations for the pharmacist.

Science.gov (United States)

Chernin, Eric L

2004-10-15

Types of economic analyses used for inhaled anesthetic agents, factors to consider in calculating the cost of inhaled anesthetics, limitations of pharmacoeconomic studies of these agents, and strategies for controlling inhaled anesthetic costs are discussed. Inhaled anesthetic agents comprise a substantial component of drug budgets. Calculation of the cost of administering an inhaled anesthetic should take into consideration the cost per mL, potency, waste, concentration and duration of gas delivery, fresh gas flow rate, molecular weight, and density. The use of newer inhaled anesthetic agents with low solubility in blood and tissue provides a more rapid recovery from anesthesia than older, more soluble agents, and also provides the same level of control of depth of anesthesia at a lower fresh gas flow rate and possibly a lower cost than older agents at a higher fresh gas flow rate. A more rapid recovery may facilitate fast-track recovery and yield cost savings if it allows the completion of additional surgical cases or allows a reduction in personnel overtime expenses. Interpretation of pharmacoeconomic studies of inhaled anesthetics requires an appreciation of the limitations in methodology and ability to extrapolate results from one setting to another. Pharmacists' efforts to reduce anesthetic waste and collaborate with anesthesiologists to improve the use of these agents can help contain costs, but improving scheduling and efficiency in the operating room has a greater potential to reduce operating room costs. Much can be done to control costs of anesthetic agents without compromising availability of these agents and patient care.

Unsteady Particle Deposition in a Human Nasal Cavity during Inhalation

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Camby M.K. Se

2010-12-01

Full Text Available The present study investigates the deposition efficiency during the unsteady inhalation cycle by using Computational Fluid Dynamics (CFD. The unsteady inhalation profile was applied at the outlet of nasopharynx, which had a maximum flow rate of 40.3L/min which corresponds to an equivalent steady inhalation tidal volume flow rate of 24.6L/min. Aerodynamic particle sizes of 5μm and 20μm were studied in order to reflect contrasting Stokes numbered particle behaviour. Two particle deposition efficiencies in the nasal cavity versus time are presented. In general, the deposition of 5μm particles was much less than 20μm particles. The first 0.2 second of the inhalation cycle was found to be significant to the particle transport, since the majority of particles were deposited during this period (i.e. its residence time. Comparisons were also made with its equivalent steady inhalation flow rate which found that the unsteady inhalation produced lower deposition efficiency for both particle sizes.

Inhalation of Budesonide/Formoterol Increases Diaphragm Muscle Contractility

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Chiyohiko Shindoh

2012-01-01

Conclusions: BUD/FORM inhalation has an inotropic effect on diaphragm muscle, protects diaphragm muscle deterioration after endotoxin injection, and inhibits NO production. Increments in muscle contractility with BUD/FORM inhalation are induced through a synergistic effect of an anti-inflammatory agent and 02-agonist.

Social stigma stops adolescents from using inhalers for asthma.

Science.gov (United States)

2017-07-10

Forgetfulness, poor routines, inadequate inhaler technique, organisational difficulties and families not understanding or accepting their children's asthma are described as barriers to the use of inhalers among adolescents with asthma.

Inhaled Steroids: First Line Treatment of Adult Asthma

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André Cartier

1995-01-01

Full Text Available Corticosteroids are the most potent inhaled anti-inflammatory drugs for asthma treatment. This paper reviews the clinical evidence supporting the early use of inhaled steroids in asthma as a first line treatment. Inhaled steroids can probably alter the course of asthma, especially in mild asthmatics. Once they have been shown to improve control of asthma and even if the need for beta2-agonists is virtually nil, their use should be continued at low doses (ie, equivalent to 400 to 500 μg of budesonide or beclomethasone for at least one year before attempting to reduce the dosage.

Interpretation of positive results of a methacholine inhalation challenge and 1 week of inhaled bronchodilator use in diagnosing and treating cough-variant asthma.

Science.gov (United States)

Irwin, R S; French, C T; Smyrnios, N A; Curley, F J

1997-09-22

In diagnosing cough due to asthma, methacholine chloride inhalation challenge (MIC) interpreted in a traditional fashion has been shown to have positive predictive values from 60% to 82%. To determine whether any features of positive results of an MIC or the results of a 1-week trial of inhaled beta-agonist therapy were helpful in predicting when the cough was due to asthma. The study design was a prospective, randomized, double-blind, placebo-controlled, crossover format performed in adult, nonsmoking subjects, who were referred for diagnosis and treatment of chronic cough. The subjects had no other respiratory complaints or medical conditions for which they were taking medications, the results of baseline spirometry and chest roentgenograms were normal, and the results of MIC were positive. After obtaining baseline data, including MICs on 2 separate days, objective cough counting, and self-assessment of cough severity using a visual analog scale, subjects were randomized to receive 2 inhalations (1.3 mg) of metaproterenol sulfate or placebo by metered dose inhaler attached to a spacer device every 4 hours while awake. At 1 week, data identical to baseline were collected, and subjects received the other metered dose inhaler for 7 days. At 1 week, data identical to baseline were collected. After completion of the protocol, subjects were followed up in the clinic to observe the final response of the cough to specific therapy. Based on the disappearance of the cough with specific therapy, the cough was due to asthma in 9 of 15 subjects and nonasthma in 6 of 15 subjects. Baseline data were similar between groups. With respect to MICs, there were no significant differences between groups in the cumulative dose of methacholine that provoked a 20% decrease in forced expiratory volume in 1 second from the postsaline baseline value (PD20 values), slopes of dose-response curves, and maximal-response plateaus. Cough severity significantly improved after 1 week of

Real-life characteristics of asthma inhaler device use in South Korea

NARCIS (Netherlands)

Wan Yau Ming, S.; Rhee, C.K.; Park, H.Y.; Yoo, K.H.; Kim, D.K.; Van Boven, J.F.; Price, D.; Park, H.S.

2016-01-01

Background and Aims: Historically, dry powder inhalers (DPIs) were considered to provide better airway distribution, easier identification of empty devices, and easier handling when compared to pressurized metered dose inhalers (pMDIs). Prior research into the major handling errors with inhaler

Inhalant abuse in the youth : A reason for concern

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J Simlai

2008-01-01

Full Text Available In recent times Inhalant or Volatile substances are emerging as a major drug of abuse in the preadolescent and adolescent age group. Most of the children are from broken homes and poor backgrounds. Inhalants have serious immediate and longterm side-effects and can also cause sudden sniffing death syndrome. It is difficult to control this ever-growing problem because Inhalants or Solvents are widely available. Management issues have been discussed in the review.

Hollow crystalline straws of diclofenac for high-dose and carrier-free dry powder inhaler formulations.

Science.gov (United States)

Yazdi, Ashkan K; Smyth, Hugh D C

2016-04-11

To crystallize diclofenac (DF) from diclofenac sodium (DFNa), to micronize DF and DFNa, and to evaluate in vitro aerodynamic performance of the jet-milled formulations From the acidic titration of aqueous DFNa, DF crystals were formed and were identified using thermal analysis, spectroscopy, and X-ray powder diffraction. Following the micronization of the DF and DFNa powders, the recovered samples were imaged, and their particle size distributions were evaluated. Samples before and after jet millings were characterized, and in vitro aerodynamic performance testing was performed on the DF sample before jet milling and the DF and DFNa samples following jet milling. Hollow needles of DF were precipitated. With similar particle size distributions, the jet-milled DFNa sample from the collection bag, and the DF sample from the cyclone were used for further characterization. Despite different deposition patterns in the Next Generation Impactor, the DF hollow needles had a comparable respirable fraction percentage to the jet-milled DF and DFNa particles. However, the jet-milled DF formulation had the best in vitro aerodynamic performance. Hollow, crystalline needles of DF were formed and possessed promising aerosol performance in comparison with the jet-milled powders. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigating the effect of artists’ paint formulation on degradation rates of TiO2‑based oil paints

NARCIS (Netherlands)

van Driel, B.A.; van den Berg, K. J.; Smout, M.; Dekker, N; Kooyman, P.J.; Dik, J.

2018-01-01

This study reports on the effect of artists’ paint formulation on degradation rates of TiO2-based oil paints. Titanium white oil paint exists in a multitude of different recipes, and the effect of the formulation on photocatalytic binder
degradation kinetics is unknown. These formulations

Pirbuterol Acetate Oral Inhalation

Science.gov (United States)

... Pirbuterol is in a class of medications called beta-agonist bronchodilators. It works by relaxing and opening ... cleaning. Once a week, remove the mouthpiece cover, turn the inhaler upside down and wipe the mouthpiece ...

Education on Correct Inhaler Technique in Pharmacy Schools ...

African Journals Online (AJOL)

Conclusion: Standard educational training may not be the most appropriate method of teaching students the correct use of inhalers. Clearly, there is a practice element missing which needs to be addressed in a feasible way. Keywords: Inhaler technique, Pharmacy education, Hands-on training, Training barrier ...

Assessment of inhalation dose sensitivity by physicochemical properties of airborne particulates containing naturally occurring radioactive materials

Energy Technology Data Exchange (ETDEWEB)

Kim, Si Young; Choi, Cheol Kyu; Kim, Yong Geon; Choi, Won Chul; Kim, Kwang Pyo [Kyung Hee University, Seoul (Korea, Republic of)

2015-12-15

Facilities processing raw materials containing naturally occurring radioactive materials (NORM) may give rise to enhanced radiation dose to workers due to chronic inhalation of airborne particulates. Internal radiation dose due to particulate inhalation varies depending on particulate properties, including size, shape, density, and absorption type. The objective of the present study was to assess inhalation dose sensitivity to physicochemical properties of airborne particulates. Committed effective doses to workers resulting from inhalation of airborne particulates were calculated based on International Commission on Radiological Protection 66 human respiratory tract model. Inhalation dose generally increased with decreasing particulate size. Committed effective doses due to inhalation of 0.01μm sized particulates were higher than doses due to 100μm sized particulates by factors of about 100 and 50 for {sup 238}U and {sup 230}Th, respectively. Inhalation dose increased with decreasing shape factor. Shape factors of 1 and 2 resulted in dose difference by about 18 %. Inhalation dose increased with particulate mass density. Particulate mass densities of 11 g·cm{sup -3} and 0.7 g·cm{sup -3} resulted in dose difference by about 60 %. For {sup 238}U, inhalation doses were higher for absorption type of S, M, and F in that sequence. Committed effective dose for absorption type S of {sup 238}U was about 9 times higher than dose for absorption F. For {sup 230}Th, inhalation doses were higher for absorption type of F, M, and S in that sequence. Committed effective dose for absorption type F of {sup 230}Th was about 16 times higher than dose for absorption S. Consequently, use of default values for particulate properties without consideration of site specific physiochemical properties may potentially skew radiation dose estimates to unrealistic values up to 1-2 orders of magnitude. For this reason, it is highly recommended to consider site specific working materials and

Food hypersensitivity by inhalation

Directory of Open Access Journals (Sweden)

Bahna Sami L

2009-02-01

Full Text Available Abstract Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization.

Effects of Radon inhalation on physiology and disorders

International Nuclear Information System (INIS)

Yamaoka, Kiyonori; Komoto, Yoshiaki

1998-01-01

In the first study, we administered Radon (Rn) to rabbits by inhalation and examined changes in the lipid peroxide (thiobarbituric acid reacting substances; TBARS) level, superoxide dismutase (SOD) activity and membrane fluidity in various organs to clarify the therapeutic effects of Rn. In the second study, we sprayed Rn spring water of various concentrations to rabbits to make the animals inhale them, and examined mainly the responses of biogenic amine neurotransmitters for clarifying the effects of Rn inhalation in the neuronal transmitter system. In the third study, indications for treatment at the Misasa Hot Spring, a Rn producing radioactive spring, include hypertension, diabetes mellitus and pain. To clarify its mechanisms of action on these conditions, we evaluated dynamic changes in blood components such as vasoactive substances after Rn inhalation. Vasodilation, alleviation of diabetic symptoms and morphine-like analgesic effects were observed, suggesting that these changes constitute part of the mechanisms of the Rn spring therapy on the above conditions. (J.P.N.)

Minimizing variability of cascade impaction measurements in inhalers and nebulizers.

Science.gov (United States)

Bonam, Matthew; Christopher, David; Cipolla, David; Donovan, Brent; Goodwin, David; Holmes, Susan; Lyapustina, Svetlana; Mitchell, Jolyon; Nichols, Steve; Pettersson, Gunilla; Quale, Chris; Rao, Nagaraja; Singh, Dilraj; Tougas, Terrence; Van Oort, Mike; Walther, Bernd; Wyka, Bruce

2008-01-01

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD).

Phototoxicity free quantum dot-based niosome formulation for controlled drug release and its monitoring

Science.gov (United States)

Kumar, Sunil; Kang, T. W.; Bala, Suman; Kamboj, Sunil; Jeon, H. C.

2018-04-01

A novel niosomes-based system composed of Hypromellose (HPMC) functionalized fluorescent, biocompatible ZnS:Mn quantum dots (QDs), and anti-HIV drug Tenofovir disoproxil fumarate (TDF) was designed. An appropriate ratio of surfactant Sorbitan Monostearate (SPAN-60) and cholesterol was used to obtain an optimal entrapment efficiency. Initially, after observing the successful interaction of HPMC with SPAN-60, the noisome formulation including (QDs + drug) and HPMC-coated QDs was synthesized by a wet chemical route and characterized by X-ray diffraction (XRD), Transmission electron microscope (TEM) and Selected Electron Diffraction (SAED). Secondly, (QDs + drug) loaded niosome formulations were studied by varying the ratio of SPAN-60 and cholesterol. Multiple studies were done to characterize the shape, size, viscosity, colloidal stability, and entrapment efficiency of (QDs + drug) loaded niosomes. Lastly, pH-dependent (QDs + drug) release profiles were studied by a spectroscopic technique considering the pH of the human gastrointestinal region to obtain the formulation stability of (QDs + drug) release from the niosome vesicles. These studies also include pH-dependent photo-stability measurements based on laser-induced multiphoton excitation technique in the Infrared region. The multiphoton time-resolved studies were completed to avoid the UV induced phototoxicity in the drug delivery modules. Current studies on the formulation of niosomes-based (QDs + drug) system laid a foundation to make a complete phototoxicity free system for tracking controlled drug release and its imaging.

Basic study on positive effects of radon inhalation on pet's health

International Nuclear Information System (INIS)

Kataoka, Takahiro; Sakoda, Akihiro; Kawabe, Atsushi; Hanamoto, Katsumi; Yamaoka, Kiyonori; Tokunaga, Rikizo

2012-01-01

Radon inhalation using our radon exposure device activated anti-oxidative function in some organs of mouse. To assess the possibility of its application to veterinary care, healthy dogs and cats with chronic renal failure were inhaled radon at a concentration of 5500 Bq/m 3 for 30 minutes every 2 days for 30 days. In result, radon inhalation within a relatively long time period significantly decreased the triglyceride level of dogs. On the other hand, some cats increased the volume of drinking water by radon inhalation and the creatinine level in blood of these cats was decreased to normal level. These findings suggest that radon inhalation may have curative properties against chronic renal failure. (author)

Inhalation toxicity of indoor air pollutants in Drosophila melanogaster using integrated transcriptomics and computational behavior analyses

Science.gov (United States)

Eom, Hyun-Jeong; Liu, Yuedan; Kwak, Gyu-Suk; Heo, Muyoung; Song, Kyung Seuk; Chung, Yun Doo; Chon, Tae-Soo; Choi, Jinhee

2017-06-01

We conducted an inhalation toxicity test on the alternative animal model, Drosophila melanogaster, to investigate potential hazards of indoor air pollution. The inhalation toxicity of toluene and formaldehyde was investigated using comprehensive transcriptomics and computational behavior analyses. The ingenuity pathway analysis (IPA) based on microarray data suggests the involvement of pathways related to immune response, stress response, and metabolism in formaldehyde and toluene exposure based on hub molecules. We conducted a toxicity test using mutants of the representative genes in these pathways to explore the toxicological consequences of alterations of these pathways. Furthermore, extensive computational behavior analysis showed that exposure to either toluene or formaldehyde reduced most of the behavioral parameters of both wild-type and mutants. Interestingly, behavioral alteration caused by toluene or formaldehyde exposure was most severe in the p38b mutant, suggesting that the defects in the p38 pathway underlie behavioral alteration. Overall, the results indicate that exposure to toluene and formaldehyde via inhalation causes severe toxicity in Drosophila, by inducing significant alterations in gene expression and behavior, suggesting that Drosophila can be used as a potential alternative model in inhalation toxicity screening.

Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

International Nuclear Information System (INIS)

Belinsky, S.A.; Hoover, M.D.; Bradley, P.L.

1994-11-01

This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database

Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

Energy Technology Data Exchange (ETDEWEB)

Belinsky, S. A.; Hoover, M. D.; Bradley, P. L. [eds.

1994-11-01

This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

Formulation of insecticide profenofos using Surfactant Diethanolamide (DEA) based on palm olein

Science.gov (United States)

Dewi, H. S.; Rahayuningsih, M.; Hambali, E.

2017-05-01

Soybean is one of the major food commodities in Indonesia that the consumption is increasing each year, but this is not in line with the domestic soybean production capacity. One cause of the low production capacity is the armyworm attact. Generally, the armyworm attack controled by spread insecticide profenofos. Profenofos need to be dissolved, but profenofos couldn’t dissolved in water. So that, it need the right formulation between the solvent and other ingredients which can supprotprofenofos performance. One of that ingredient is surfactant. This research used surfactant diethanolamide (DEA) based on palm olein. DEAfunction in insecticide formulation are as homogenizer, dispersant, sticker and spreader agent.The aims of this research are to obtain the best emultion insecticide product based on profenofos as the active ingredients and DEA as the surfactant, moreover it also to obtain information of the physico-chemical properties. The formulation test performed with compeletely randomized design (CRD) with two factors, first factor is DEA concentrationand the second factor is profenofos concentration. Data of physico-chemical properties test was analyzed by analysis of variance (ANOVA) and significant result tested by Duncant Multiple Range Test (DMRT).The result showed that, surfactant DEA could make good emultion between profenofos and sodium ethoxide as the solvent. The best treatment which obtain from formulation stage is concentrate with DEA 10% and profenofos 40%. Physico-chemical properties test result showed that droplet size is 1,76-2,07 µm, contact angle 11,575-24,218°, density 0,996-0,998 g/cm3, surface tension 16,56-40,72 dyne/cm, viscosity 1,032-1,078 Cp and pH 6,87-8,22.

Fatty acid-based formulations for wood protection against mold and sapstain

Science.gov (United States)

Carol A. Clausen; Robert D. Coleman; Vina W. Yang

2010-01-01

Safer, highly effective biocides providing long-term protection of mold growth on wood-based materials is of interest to the wood protection industry. Moldicide formulations containing synergistic combinations of ingredients derived from natural sources are commonly recognized as a promising approach for the next generation of wood protectants. Although fatty acid (FA...

The chemo and the mona : Inhalants, devotion and street youth in Mexico city

NARCIS (Netherlands)

Gigengack, Roy

This paper understands inhalant use - the deliberate inhalation of volatile solvents or glues with intentions of intoxication - as a socially and culturally constituted practice. It describes the inhalant use of young street people in Mexico City from their perspective ("the vicioso or inhalant

Effectiveness of the different methods of inhalation drugs delivery in children with bronchial asthma

Directory of Open Access Journals (Sweden)

S.M. Nedelska

2017-02-01

Full Text Available Aim of the work — to evaluate the effectiveness of inhalation technique when using different types of inhalers (dry powder inhalers — Turbuhaler, Diskus, metered-dose inhalers, breath-actuated inhalers — Easyhaler. Materials and methods. 45 patients aged 6–17 years underwent the evaluation of inhalation technique accuracy with the use of In-Check-Dial — apparatus, which imitates the airway resistance that should be overcome during inspiration through different inhaler types, and measure inspiration velocity. Incidence of mistakes was studied in different age groups. Results. 80 % of children aged 6–7 years made mistakes while using Turbuhaler, 73.3 % — metered-dose inhaler, 60 % — Easyhaler. There were no mistakes in patients making inhalation by means of Diskhaler. 100 % of children aged 12–14 years incorrectly used metered-dose inhaler. Easyhaler was incorrectly used in 66.6 % of cases, Diskhaler — in 26.6 %. Among elder group, incidence of mistakes when making inhalations through Turbuhaler was lower — 40 % in 12–14-year-old group and 25 % — in 15–17-year-old (р < 0.05. Children of 15–17 years old are able to use Turbuhaler and Diskus (mistakes in 33.3 and 46.6 %, respectively. At the same time, none of the patients have done the correct inhalation by means of metered-dose inhaler, 93.3 % of the patients have mistakes when using Easyhaler. Conclusions. The incidence of mistakes depends on the age and inhaler type and reaches 26–100 %. Minimal quantity of mistakes is seen for Diskus (in all age groups, maxi­mal — for metered-dose inhaler. For the purpose of optimal inhaler choice in a child with bronchial asthma, it is advisable to measure the inspiratory flow with the help of In-Check-Dial before therapy administration.

Formulation and evaluation of microemulsion-based hydrogel for topical delivery.

Science.gov (United States)

Sabale, Vidya; Vora, Sejal

2012-07-01

The purpose of this study was to develop microemulsion-based hydrogel formulation for topical delivery of bifonazole with an objective to increase the solubility and skin permeability of the drug. Oleic acid was screened as the oil phase of microemulsions, due to a good solubilizing capacity of the microemulison systems. The pseudo-ternary phase diagrams for microemulsion regions were constructed using oleic acid as the oil, Tween 80 as the surfactant and isopropyl alcohol (IPA) as the cosurfactant. Various microemulsion formulations were prepared and optimized by 3(2) factorial design on the basis of percentage (%) transmittance, globule size, zeta potential, drug release, and skin permeability. The abilities of various microemulsions to deliver bifonazole through the skin were evaluated ex vivo using Franz diffusion cells fitted with rat skins. The Hydroxy Propyl Methyl Cellulose (HPMC) K100 M as a gel matrix was used to construct the microemulsion-based hydrogel for improving the viscosity of microemulsion for topical administration. The optimized microemulsion-based hydrogel was evaluated for viscosity, spreadability, skin irritancy, skin permeability, stability, and antifungal activity by comparing it with marketed bifonazole cream. The mechanism of drug release from microemulsion-based hydrogel was observed to follow zero order kinetics. The studied optimized microemulsion-based hydrogel showed a good stability over the period of 3 months. Average globule size of optimized microemulsion (F5) was found to be 18.98 nm, zeta potential was found to be -5.56 mv, and permeability of drug from microemulsion within 8 h was observed 84%. The antifungal activity of microemulsion-based hydrogel was found to be comparable with marketed cream. The results indicate that the studied microemulsion-based hydrogel (F5) has a potential for sustained action of drug release and it may act as promising vehicle for topical delivery of ibuprofen.

Factors associated with appropriate inhaler use in patients with COPD – lessons from the REAL survey

Directory of Open Access Journals (Sweden)

Price D

2018-02-01

Full Text Available David Price,1,2 Dorothy L Keininger,3 Boomi Viswanad,4 Matthias Gasser,5 Susann Walda,5 Florian S Gutzwiller3 1Division of Applied Health Sciences, Academic Primary Care, University of Aberdeen, Aberdeen, UK; 2Observational and Pragmatic Research Institute, Singapore; 3Novartis Pharma AG, Basel, Switzerland; 4Novartis Healthcare Pvt. Ltd., Hyderabad, India; 5GfK Switzerland AG, Basel, Switzerland Background: Nonadherence to medication and incorrect use of inhalers represent significant barriers to optimal disease management of patients with chronic obstructive pulmonary disease (COPD. Thus, health care professionals (HCPs play a critical role in educating their patients on appropriate inhaler use and in ensuring medication adherence. However, many patients do not receive appropriate inhaler training or have not had their inhaler technique checked.Methods: The Real-life Experience and Accuracy of inhaLer use (REAL survey was a computer-assisted, telephonic survey consisting of 23 questions gathering real-world information on correct inhaler use, inhalation technique, device attributes, adherence, dosing accuracy, training, correct device use, ease of use, and factors that influence patient adherence in commercially available inhalers delivering COPD maintenance therapy. All results are based on patient-reported data.Results: The survey was conducted between January 4, 2016 and February 2, 2016. A total of 764 patients using various inhalers (Breezhaler® =186; Ellipta® =191; Genuair® =194; Respimat® =201 with mild to very severe COPD, with a mean ± SD age 56±9.8 years, completed the survey. Patient self-reported adherence was significantly lower in younger patients compared to older patients (p=0.020. Eighty-three percent of patients indicated that a demonstration (in-person was “very helpful” versus 58% for video. Patient preferences for training methods were as follows: demonstration of inhaler use (83%, video (58%, instructions for

Derived ERLs for inhalation of alpha-emitting aerorols

International Nuclear Information System (INIS)

Macdonald, H.F.

1977-01-01

Derived alpha action levels are expressed as dpm/m 3 and give the airborne concentration of an assumed mixture of α-emitters which if inhaled for a period of 4 hours would result in a dose commitment to members of the critical group in the exposed population equal to the emergency reference levels (ERLs) of dose recommended by the Medical Research Council (1975). The period of 4 hours is chosen as a realistic time during which an assessment of the severity of a release may be made and appropriate countermeasures instituted. The derived α ERLs are set with reference to the potential range of isotopic releases for a specific reactor system and in the case of gas-cooled magnox reactors, a value of 10 3 dpm/m 3 (170 Bqm -3 ) has been used. This level was based upon the lung and GI tract models originally recommended by ICRP 2 (1959:1964) and revised ERLs for the inhalation of α-emitters consequent upon the improved metabolic models subsequently proposed by the ICRP (1966:1972) are evaluated. It is shown that the derived α ERLs for irradiated magnox and AGR fuels are largely independent of the physico-chemical forms of the released material, while variations with cooling time of fuel are also discussed. In addition, the special limits imposed by the chemical toxicity of uranium when inhaled in a soluble, low enriched form are briefly outlined

Experiment of aerosol-release time for a novel automatic metered dose inhaler

Directory of Open Access Journals (Sweden)

Mingrong Zhang

2016-05-01

Full Text Available The objective of this study was to evaluate the aerosol-release time in the development of a new automatic adapter for metered dose inhaler. With this device, regular manually operated metered dose inhalers become automatic. During the study, an inhalation simulator was designed and tested with the newly developed mechatronic system. By adjusting the volume and the pressure of the vacuum tank, most human inhalation waveforms were able to simulate. As an example, regular quick-deep and slow-deep waveforms were matched within reasonable accuracy. Finally, with the help of dynamic image processing, the aerosol-release time (Tr was carefully measured and fully discussed, including the switch-on time (Ts, the mechatronics-hysteresis (Tm and the intentional-delay (Ti. Under slow-deep inhalation condition which is suitable for metered dose inhaler medicine delivery, the switch-on flow-rate could reach as low as 10 L/min, and the corresponding switch-on time was approximately 0.20 s. While the mechatronics-hysteresis depended on the brand of metered dose inhaler, assuming there was no intentional-delay, the aerosol-release time could be as low as 0.40 and 0.60 s, respectively, for two commercially available metered dose inhalers studied in this article. Therefore, this newly developed mechatronic adapter system could ensure aerosol-release time (Tr within satisfactory range for metered dose inhalers.

Novel jojoba oil-based emulsion gel formulations for clotrimazole delivery.

Science.gov (United States)

Shahin, Mostafa; Hady, Seham Abdel; Hammad, Mohammed; Mortada, Nahed

2011-03-01

Jojoba oil-based emulgel formulations were prepared using different concentrations of various gelling agents, such as hydroxypropyl methylcellulose (HPMC) and Carbopol 934 P and combination of both. The prepared emulgels were physically evaluated for their stability after temperature cycle test, centrifugation and long-term shelf storage for 1 year at room temperature. The in vitro release at 37 °C was studied to define the effect of the concentration and type of the gelling agent. A comparison between the formulated emulgels and two commercially available products, Candistan® and Canesten® creams, was carried out to judge their efficacy and stability. The prepared emulgels exhibited non-Newtonian shear thinning behavior with little or no thixotropy. Four emulgels showed excellent stability as they demonstrated consistent rheological model under different treatment conditions. The in vitro release test showed variation in the extent of percent drug released. The drug release from the commercial preparation was lower than some of the prepared emulgel formulae. One formula containing combination of the two gelling agents (HPMC and Carbopol 934 P), showed excellent stability and high extent of clotrimazole release was microbiologically evaluated against Candida albicans using cylinder and plate method. The selected formula showed superior antimycotic activity compared to the commercially available formulation. Further in vivo animal studies for the obtained stable formula is recommended. © 2011 American Association of Pharmaceutical Scientists

PMDY METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

Oxidative stress in a rat model of cotton smoke inhalation-induced ...

African Journals Online (AJOL)

Background: Smoke inhalation injury refers to airway and lung parenchyma injury and general chemical damage caused by inhaling toxic gases and substances. The aim of this study was to explore the oxidative stress mechanism of cotton smoke inhalation-induced pulmonary injury in a rat model. Materials and Methods: ...

Dose-Dependent Protective Effect of Inhalational Anesthetics Against Postoperative Respiratory Complications

DEFF Research Database (Denmark)

Grabitz, Stephanie D; Farhan, Hassan N; Ruscic, Katarina J

2017-01-01

OBJECTIVES: Inhalational anesthetics are bronchodilators with immunomodulatory effects. We sought to determine the effect of inhalational anesthetic dose on risk of severe postoperative respiratory complications. DESIGN: Prospective analysis of data on file in surgical cases between January 2007...... with endotracheal intubation. INTERVENTIONS: Median effective dose equivalent of inhalational anesthetics during surgery (derived from mean end-tidal inhalational anesthetic concentrations). MEASUREMENTS AND MAIN RESULTS: Postoperative respiratory complications occurred in 6,979 of 124,497 cases (5.61%). High...... inhalational anesthetic dose of 1.20 (1.13-1.30) (median [interquartile range])-fold median effective dose equivalent versus 0.57 (0.45-0.64)-fold median effective dose equivalent was associated with lower odds of postoperative respiratory complications (odds ratio, 0.59; 95% CI, 0.53-0.65; p

Dosage of DTPA administration by inhalation

International Nuclear Information System (INIS)

Koizumi, Akira; Fukuda, Satoshi; Yamada, Yuji; Iida, Haruzo; Shimo, Michikuni

2000-01-01

The administration of DTPA by inhalation was examined as an emergency medical treatment. In order to estimate the practical dosage to the human, an accurate model of the human air way was connected to a anesthetizer and respiration was simulated. Ca-DTPA, aerosolized by an ultra-sonic nebulizer, was administered by inhalation to the model. For the experiments, the respiratory volume (tidal volume) and the respiration rate was 12 per minute. Irrigation water from the model of larynx and mouth, and the air filter were collected and measured by chelate titration in order to determine the quantity of aerosolized DTPA and the amount deposited on the trachea and lang. The results indicated that the quantity of aerosolized DTPA varied with dilution of the DTPA solution in a ample. It was found that a 3 time dilution was the most practical and that 73 mg of DTPA per minute could be aerosolized. Furthermore, the results indicated that 46% of the aerosolized DTPA was taken in through inhalation and that 26% of DTPA was deposited in the trachea and lung. These results suggest that in practical application in the emergency medical treatment, 15 minutes of inhalation could delivered to approximately 500 mg of DTPA, and 130 mg could be delivered to the trachea and lung. It is considered that these quantity are enough amount to increase the effects of radioactive nuclides from the body, comparing with the recommended dosage for injection administration. (author)

Inhalation dose due to indoor radon and thoron concentrations in the surrounding villages of Hyderabad, Andhra Pradesh, India

International Nuclear Information System (INIS)

Sreenath Reddy, M.; Sreenivasa Reddy, B.; Yadagiri Reddy, P.; Gopal Reddy, Ch.; Rama Reddy, K.

2006-01-01

Inhalation of radon, thoron and their decay products is the major contribution to the total radioactive dose received by the human population from the natural radiation. The indoor inhalation doses due to radon, thoron and their progenies in the surrounding villages of Hyderabad, India are evaluated. The average inhalation dose due to radon and its progeny is found to be 0.26 ± 0.21 mSv y -1 and due to thoron and its progeny is 0.35 ± 0.38 mSv y -1 . The inhalation dose is also analyzed based on the types of floor, roof and walls of the dwellings and it is found that the dwellings with mud type construction materials have higher inhalation dose. Generally, the contribution of thoron and its progeny to the total dose is neglected but in the present study area the fractional dose of thoron and its progeny is found to be comparable to that of radon and its progeny. (author)

Fourier transform-infrared spectroscopy as a diagnostic tool for mosquito coil smoke inhalation toxicity in Swiss Albino mice

Science.gov (United States)

Anusha, Chidambaram; Sankar, Renu; Varunkumar, Krishnamoorthy; Sivasindhuja, Gnanasambantham; Ravikumar, Vilwanathan

2017-12-01

The goal of this study is to establish Fourier transform-infrared (FTIR) spectroscopy as a diagnostic tool for allethrin-based mosquito coil smoke inhalation induced toxicity in mice. Primarily, we confirmed mosquito coil smoke inhalation toxicity in mice via reduced the body, organ weight and major vital organ tissue morphological structure changes. Furthermore, FTIR spectra was collected from control and mosquito coil smoke inhalation (8 h per day for 30 days) mice various tissues like liver, kidney, lung, heart and brain, to investigate the functional groups and their corresponding biochemical content variations. The FTIR spectra result shown major bio macromolecules such as protein and lipid functional peaks were shifted (decreased) in the mosquito coil smoke inhalation group as compared to control. The drastic peak shift was noticed in the liver, kidney followed by lung and brain. It is therefore concluded that the FTIR spectroscopy can be a successful detection tool in mosquito coil smoke inhalation toxicity.

The Chemo and the Mona: Inhalants, devotion and street youth in Mexico City

NARCIS (Netherlands)

Gigengack, R.A.

2014-01-01

This paper understands inhalant use – the deliberate inhalation of volatile solvents or glues with intentions of intoxication – as a socially and culturally constituted practice. It describes the inhalant use of young street people in Mexico City from their perspective (“the vicioso or inhalant

Cerebral blood flow (CBF) with 133Xe inhalation method

International Nuclear Information System (INIS)

Kusunoki, Tadaki; Masumura, Michio; Tamaki, Norihiko; Matsumoto, Satoshi; Yamashita, Hideyuki.

1982-01-01

The effects of CO 2 inhalation on the cerebral blood flow (CBF) were examined with 133 Xe inhalation method (Novo Inhalation Cerebrograph) on 9 normal peoples and 20 patients. Nine normal peoples were divided into 3 groups consisting of each 3 peoples, namely young age group, middle age group, and old age group. Each increased CBF (%) by CO 2 inhalation was 40 -- 44 in young age group, 36 -- 37 in middle age group, and 35 -- 36 in old age group in the blood flow of the first compartment (F 1 ), and 27 -- 28 in young age group, 30 -- 31 in middle age group and 23 -- 24 in old age group in the initial slope index (ISI). Each CO 2 reactivity factor (RF) was 5.5 -- 5.8 in young age group, 3.8 -- 4.0 in middle age group and 3.3 in old age group in F 1 , and 3.1 -- 3.2 in young age group, 2.0 -- 3.3 in middle age group, and 1.2 -- 1.3 in old age group in ISI. Twenty patients consisted of 15 patients of occlusive cerebrovascular disease, 2 patients of head injury, 2 patients of normal pressure hydrocephalus and one patient of subarachnoid hemorrhage. RF was abnormally lower than normal value in 5 patients in F 1 , but in 7 in ISI. Clinical benefits of CBF study during CO 2 inhalation with 133 Xe inhalation method were discussed. (author)

Accidental Cutaneous Burns Secondary to Salbutamol Metered Dose Inhaler

Directory of Open Access Journals (Sweden)

Ashutosh Kale

2010-01-01

Full Text Available We report a case of accidental cutaneous burns caused by salbutamol metered dose inhaler. A 9-year-old boy underwent dental extraction at a children's hospital and was incidentally noted to have burn injuries on dorsum of both hands. On questioning, the boy revealed that a few days ago his 14-year-old brother, who is an asthmatic, playfully sprayed his salbutamol metered dose inhaler on the back of both his hands with the inhaler's mouth piece being in direct contact with the patient's skin. On examination, there was a rectangular area of erythema with superficial peeling on the dorsum of both hands, the dimensions of which exactly matched those of the inhaler's mouthpiece. It is possible that the injury could have been a chemical burn from the pharmaceutical/preservative/propellant aerosol or due to the physical effect of severe cooling of the skin or mechanical abrasive effect of the aerosol blasts or a combination of some or all the above mechanisms. This case highlights the importance of informing children and parents of the potentially hazardous consequences of misusing a metered dose inhaler.

Assessing human exposure risk to cadmium through inhalation and seafood consumption

International Nuclear Information System (INIS)

Ju, Yun-Ru; Chen, Wei-Yu; Liao, Chung-Min

2012-01-01

Highlights: ► Trophically available fraction in seafood and bioaccessibility is linked. ► Human health risk to Cd can via inhalation and seafood consumption. ► Female had the higher Cd accumulation in urine and blood than male. ► Cigarette smoking is a major determinant of human Cd intake. - Abstract: The role of cadmium (Cd) bioaccessibility in risk assessment is less well studied. The aim of this study was to assess human health risk to Cd through inhalation and seafood consumption by incorporating bioaccessibility. The relationships between trophically available Cd and bioaccessibility were constructed based on available experimental data. We estimated Cd concentrations in human urine and blood via daily intake from seafood consumption and inhalation based on a physiologically-based pharmacokinetic (PBPK) model. A Hill-based dose–response model was used to assess human renal dysfunction and peripheral arterial disease risks for long-term Cd exposure. Here we showed that fish had higher bioaccessibility (∼83.7%) than that of shellfish (∼73.2%) for human ingestion. Our results indicated that glomerular and tubular damage among different genders and smokers ranged from 18.03 to 18.18%. Our analysis showed that nonsmokers had 50% probability of peripheral arterial disease level exceeding from 3.28 to 8.80%. Smoking populations had 2–3 folds higher morbidity risk of peripheral arterial disease than those of nonsmokers. Our study concluded that the adverse effects of Cd exposure are exacerbated when high seafood consumption coincides with cigarette smoking. Our work provides a framework that could more accurately address risk dose dependency of Cd hazard.

Direct-reading inhalable dust monitoring--an assessment of current measurement methods.

Science.gov (United States)

Thorpe, Andrew; Walsh, Peter T

2013-08-01

Direct-reading dust monitors designed specifically to measure the inhalable fraction of airborne dust are not widely available. Current practice therefore often involves comparing the response of photometer-type dust monitors with the concentration measured with a reference gravimetric inhalable sampler, which is used to adjust the dust monitor measurement. However, changes in airborne particle size can result in significant errors in the estimation of inhalable concentration by this method. The main aim of this study was to assess how these dust monitors behave when challenged with airborne dust containing particles in the inhalable size range and also to investigate alternative dust monitors whose response might not be as prone to variations in particle size or that could be adapted to measure inhalable dust concentration. Several photometer-type dust monitors and a Respicon TM, tapered element oscillating microbalance (TEOM) personal dust monitor (PDM) 3600, TEOM 1400, and Dustrak DRX were assessed for the measurement of airborne inhalable dust during laboratory and field trials. The PDM was modified to allow it to sample and measure larger particles in the inhalable size range. During the laboratory tests, the dust monitors and reference gravimetric samplers were challenged inside a large dust tunnel with aerosols of industrial dusts known to present an inhalable hazard and aluminium oxide powders with a range of discrete particle sizes. A constant concentration of each dust type was generated and peak concentrations of larger particles were periodically introduced to investigate the effects of sudden changes in particle size on monitor calibration. The PDM, Respicon, and DataRam photometer were also assessed during field trials at a bakery, joinery, and a grain mill. Laboratory results showed that the Respicon, modified PDM, and TEOM 1400 observed good linearity for all types of dust when compared with measurements made with a reference IOM sampler; the

Silicate Based Glass Formulations for Immobilization of U.S. Defense Wastes Using Cold Crucible Induction Melters

Energy Technology Data Exchange (ETDEWEB)

Smith, Gary L.; Kim, Dong-Sang; Schweiger, Michael J.; Marra, James C.; Lang, Jesse B.; Crum, Jarrod V.; Crawford, Charles L.; Vienna, John D.

2014-05-22

The cold crucible induction melter (CCIM) is an alternative technology to the currently deployed liquid-fed, ceramic-lined, Joule-heated melter for immobilizing of U.S. tank waste generated from defense related reprocessing. In order to accurately evaluate the potential benefits of deploying a CCIM, glasses must be developed specifically for that melting technology. Related glass formulation efforts have been conducted since the 1990s including a recent study that is first documented in this report. The purpose of this report is to summarize the silicate base glass formulation efforts for CCIM testing of U.S. tank wastes. Summaries of phosphate based glass formulation and phosphate and silicate based CCIM demonstration tests are reported separately (Day and Ray 2013 and Marra 2013, respectively). Combined these three reports summarize the current state of knowledge related to waste form development and process testing of CCIM technology for U.S. tank wastes.

Dose-effect studies with inhaled plutonium in beagles

International Nuclear Information System (INIS)

Anon.

1982-01-01

Data are presented for all dogs employed in current life-span dose effect studies with inhaled 239 PuO 2 , and 239 Pu nitrate. Information is presented on the estimated initial alveolar deposition, based on external thorax counts and on estimated lung weights at time of exposure. Information is also provided on the current interpretation of the most prominent clinical-pathological features associated with the death of animals

Estimation of the acute inhalation hazards of chemicals based on route-to-route and local endpoint extrapolation: Experience from Bulk Maritime Transport

NARCIS (Netherlands)

Höfer, T.; James, D.; Syversen, T.; Bowmer, T.

2011-01-01

Data on acute lethal inhalation toxicity from animal studies are commonly required for assessing the hazards to human health of volatile, gaseous and dusty chemicals or their mixtures. The International Maritime Organisation (IMO) made the provision of acute inhalation toxicity data a mandatory

Cow Dung Ingestion and Inhalation Dependence: A Case Report

Science.gov (United States)

Khairkar, Praveen; Tiple, Prashant; Bang, Govind

2009-01-01

Although abuse of several unusual inhalants had been documented, addiction to cow dung fumes or their ashes has not been reported in medical literature as yet. We are reporting a case of cow dung dependence in ingestion and inhalational form.

Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

OpenAIRE

Gladwin, Mark T.; Schechter, Alan N.; Shelhamer, James H.; Pannell, Lewis K.; Conway, Deirdre A.; Hrinczenko, Borys W.; Nichols, James S.; Pease-Fye, Margaret E.; Noguchi, Constance T.; Rodgers, Griffin P.; Ognibene, Frederick P.

1999-01-01

Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of β-chain cysteine 93, raise the possibilty of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P50, did not respo...

Self-reported osteoporosis prevention in inhaled corticosteroid users in community pharmacy setting

Directory of Open Access Journals (Sweden)

Valerie Chan

2015-05-01

Full Text Available Objectives: The use of inhaled corticosteroids is the standard maintenance therapy in asthma therapy and as adjunct therapy in moderate to severe chronic obstructive pulmonary disease. A dose-related increase in fracture risk is associated with inhaled corticosteroid use; there is an inverse relationship between bone mineral density and duration and cumulative dose of inhaled corticosteroid. Adequate intake of calcium and vitamin D are cornerstones of osteoporosis prevention. The objectives are to assess whether the proportion of patients receiving inhaled corticosteroids are taking calcium and vitamin D; the association between long-term inhaled corticosteroid use and abnormal bone mineral density or fractures; and how many qualified patients received bone mineral density scans. Methods: Patients who filled a prescription for inhaled corticosteroids at selected community pharmacies across Alberta were recruited for a survey of their osteoporosis prevention activities. Results: A total of 256 patients from 12 community pharmacies were included. The average age was 60 ± 17.4 years with 65% female. There were 21%, 51%, and 28% of patients on high, medium, and low dose inhaled corticosteroids, respectively. Only 17% of patients >50 years old received recommended calcium and vitamin D supplementation and 87 (73% of the qualified patients received bone mineral density scan. Conclusion: Osteoporosis prevention in inhaled corticosteroid users is currently poorly addressed. More promotion is needed to raise pharmacist awareness of the risks of inhaled corticosteroids.

Electrochemical and dissolution studies on coated film and magnetite pellet in PDCA and NTA based formulations

International Nuclear Information System (INIS)

Srinivasan, M.P.; Sumathi, S.; Rangarajan, S.; Narasimhan, S.V.

2000-01-01

In water cooled nuclear reactors magnetite often exists as both mobile particulate protective film on the inner surface of the PHT system. To determine the mechanism and kinetics of dissolution from a film coated on carbon steel (CS) and magnetite pellet electrochemical measurements were carried out in 2,6-pyridine dicarboxylic acid (PDCA) and nitrilo-triacetic acid (NTA) based formulations containing ascorbic acid (AA) and citric acid (CA) at 28 degC and 60 degC. The solution redox potential arises based on the release of relative amounts of Fe 2+ and Fe 3+ . Complexation, adsorption and reduction affect the concentration of these species in solutions. On coated specimen, the pore size and rate of formation via auto reduction contribute to the observed potential. In PDCA based formulation higher percentage of magnetite dissolution with lower base metal corrosion was observed as compared to that in NTA based formulation. The base metal aided dissolution due to the pores and microcracks in the film (Auto reduction) was observed for coated film. The dominant role of surface adsorption characteristics of PDCA, AA and CA were evident in magnetite pellet dissolution studies. (author)

Cancer hazard from inhaled plutonium

International Nuclear Information System (INIS)

Gofman, J.W.

1975-01-01

The best estimate of the lung cancer potential in humans for inhaled insoluble compounds of plutonium (such as PuO 2 particles) has been grossly underestimated by such authoritative bodies as the International Commission on Radiological Protection and the British Medical Research Council. Calculations are presented of lung cancer induction by 239 Pu as insoluble particles and for deposited reactor-grade Pu. The reason for the gross underestimate of the carcinogenic effects of Pu by ICRP or the British Medical Research Council (BMRC) is their use of a totally unrealistic idealized model for the clearance of deposited Pu from the lungs and bronchi plus their non-recognition of the bronchi as the true site for most human lung cancers. The erroneous model used by such organizations also fails totally to take into account the effect of cigarette-smoking upon the physiological function of human lungs. Plutonium nuclides, such as 239 Pu, or other alpha particle-emitting nuclides, in an insoluble form represent an inhalation cancer hazard in a class some 100,000 times more potent than the potent chemical carcinogens, weight for weight. The already-existing lung cancer data for beagle dogs inhaling insoluble PuO 2 particles is clearly in order of magnitude agreement with calculations for humans

Proposed retention model for human inhalation exposure to 241AmO2

International Nuclear Information System (INIS)

Mewhinney, J.A.; Griffith, W.C.; Muggenburg, B.A.

1980-01-01

A dosimetry model based on a four-year study in Beagle dogs was developed to predict patterns of absorbed radiation doses for people exposed by inhalation to 241 AmO 2 . Following a single inhalation exposure to one of three sizes of monodisperse or a polydisperse aerosol of 241 AmO 2 , pairs of dogs were sacrificed at 8, 32, 64 and 256 days, and 2 and 4 years. For about 80% of the initial lung burden, the retention halftimes were 11, 18, 26 and 27 days for the 0.75, 1.5 and 3.0 μm aerodynamic diameter and the 1.8 μm activity median aerodynamic diameter aerosols, respectively. For the remaining 20% of the initial lung burden, the retention halftimes were between 200 to 300 days with no apparent particle size influence. Additional 241 Am metabolic studies reported in the literature using inhalation exposure or injection of the citrate complex were synthesized in the model as were eleven reported cases of human inhalation exposure. This model is compared to the ICRP II and TGLD lung models, both developed by analogy to Pu metabolism. The proposed model differs from these latter models in two important areas: (a) lung retention of 241 AmO 2 could not be adapted to the classifications used in these models, and (b) the fractional translocation from lung to other organs is 2 to 8 times larger. These factors considerably alter the predicted radiation dose distribution among organs and lead to the conclusion that derived radiation protection standards for 241 AmO 2 inhalation exposure should be modified. (author)

Property Model-Based Chemcal Substitution and Chemical Formulation Design

DEFF Research Database (Denmark)

Jhamb, Spardha Virendra; Liang, Xiaodong; Hukkerikar, Amol Shivajirao

Chemical-based products including structured product formulations and single molecule products have proven to be a boon to mankind and have been a significant part of our economies. Our life and the changes around us cannot be imagined without the presence or involvement of chemicals. But like...... with environmentally benign chemicals. Additionally, the decisions taken during chemical product design also have an impact on the process and product performance and are influenced by company strategy, availability of market and government policies [2]. Hence, undoubtedly there is a need to develop a systematic...... [3] will also be highlighted. A set of new group contribution-based models for a number of useful properties of amino acids will be presented. Through examples on substitution of chemicals from chemical-based products from various sectors namely cosmetics and personal care, pharmaceutical and food...

Trends in wood dust inhalation exposure in the UK, 1985-2005.

NARCIS (Netherlands)

Galea, K.S.; van Tongeren, M.; Sleeuwenhoek, A.J.; While, D.; Graham, M.; Bolton, A.; Kromhout, H.; Cherrie, J.W.

2009-01-01

OBJECTIVES: Wood dust data held in the Health and Safety Executive (HSE) National Exposure DataBase (NEDB) were reviewed to investigate the long-term changes in inhalation exposure from 1985 to 2005. In addition, follow-up sampling measurements were obtained from selected companies where exposure

Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat; Etudes biocinetique et biologique comparees d'inhalations chroniques et aigues de composes uraniferes chez le rat

Energy Technology Data Exchange (ETDEWEB)

Monleau, M

2005-12-15

Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure. It

Experiment of aerosol-release time for a novel automatic metered dose inhaler

OpenAIRE

Mingrong Zhang; Songhao Wang; Yu-Ching Yang

2016-01-01

The objective of this study was to evaluate the aerosol-release time in the development of a new automatic adapter for metered dose inhaler. With this device, regular manually operated metered dose inhalers become automatic. During the study, an inhalation simulator was designed and tested with the newly developed mechatronic system. By adjusting the volume and the pressure of the vacuum tank, most human inhalation waveforms were able to simulate. As an example, regular quick-deep and slow-de...

Suffocation caused by plastic wrap covering the face combined with nitrous oxide inhalation.

Science.gov (United States)

Leth, Peter Mygind; Astrup, Birgitte Schmidt

2017-09-01

Suicide using a combination of a plastic bag over the head and inhalation of a non-irritating gas, such as helium, argon or nitrogen, has been reported in the literature. Here an unusual suicide method in a 17-year old man by suffocation from covering the face with household plastic wrap, combined with nitrous oxide inhalation, is presented. The case was reviewed based on police, autopsy and hospital reports. A PubMed search for scientific literature related to nitrous oxide abuse and suicide by suffocation was performed and our findings discussed in relation to the scientific literature found. The deceased was a 17-year old man who was found with the nose and mouth closed with a piece of kitchen plastic wrap. The plastic wrap had been removed prior to autopsy. Autopsy findings were suggestive of asphyxia, but were otherwise negative. Nitrous oxide was detected in the brain and lung tissue with headspace-gas chromatography-mass spectrometry (headspace-GCMS). The cause of death was assumed to be suffocation caused by plastic wrap covering the face, combined with nitrous oxide inhalation. Suicide was suspected because of a history of depression for several months. Nitrous oxide, also known as laughing gas, has a euphoric effect and is used as a recreational inhalant drug that can be purchased legally. Deaths caused by recreational nitrous oxide abuse are rare but may occur if used in combination with a plastic bag over the head. This is the first report of suicide by suffocation by external obstruction combined with nitrous oxide inhalation.

Investigation into the Manufacture and Properties of Inhalable High-Dose Dry Powders Produced by Comilling API and Lactose with Magnesium Stearate.

Science.gov (United States)

Lau, Michael; Young, Paul M; Traini, Daniela

2017-08-01

The aim of the study was to understand the impact of different concentrations of the additive material, magnesium stearate (MGST), and the active pharmaceutical ingredient (API), respectively, on the physicochemical properties and aerosol performance of comilled formulations for high-dose delivery. Initially, blends of API/lactose with different concentrations of MGST (1-7.5% w/w) were prepared and comilled by the jet-mill apparatus. The optimal concentration of MGST in comilled formulations was investigated, specifically for agglomerate structure and strength, particle size, uniformity of content, surface coverage, and aerosol performance. Secondly, comilled formulations with different API (1-40% w/w) concentrations were prepared and similarly analyzed. Comilled 5% MGST (w/w) formulation resulted in a significant improvement in in vitro aerosol performance due to the reduction in agglomerate size and strength compared to the formulation comilled without MGST. Higher concentrations of MGST (7.5% w/w) led to reduction in aerosol performance likely due to excessive surface coverage of the micronized particles by MGST, which led to failure in uniformity of content and an increase in agglomerate strength and size. Generally, comilled formulations with higher concentrations of API increased the agglomerate strength and size, which subsequently caused a reduction in aerosol performance. High-dose delivery was achieved at API concentration of >20% (w/w). The study provided a platform for the investigation of aerosol performance and physicochemical properties of other API and additive materials in comilled formulations for the emerging field of high-dose delivery by dry powder inhalation.

Surface characterization of lignocellulosics for composite manufacture

Science.gov (United States)

Iyer, Ananth V.

The objectives of this research were to form moisture resistant wheat strawboards, either by altering the straw surface characteristics or by changing the chemistry of the polymeric 4, 4' diphenylmethane diisocyanate (PMDI)-based matrix and interface. Part I compared the surface characteristics of wheat, barley, oat, rice, kenaf, hemp and softwood particles. All cereal straws had two surfaces: epidermis and brittle-pith unlike one heterogeneous type observed for bast fibers and softwood particles. The epidermis of cereal straws was not wet by water or aqueous binders, whereas the pith surface allowed the penetration of water, but was not readily wetted by aqueous binders. Between the different surface treatments evaluated for wheat straw in Part II, NaOH selectively peeled-off the epidermis and pith layers. The treated straw particles were formable into strawboards using aqueous phenol-formaldehyde, urea-formaldehyde, and duroplastic acrylic acid binders with good internal bond strength (IBS) and adequate water resistance. In Part III it was shown that, decreasing straw particle sizes and bleaching worsened the mechanical properties of strawboards, but the moisture absorption properties of bleached strawboards were lower than the unbleached ones. Layering of straw particles in strawboards did not seem to affect their mechanical or moisture absorption properties. Part IV showed that the pith surface of wheat straw was fractured on curing with PMDI, providing hollow microcrevices for water accumulation. Furthermore, the cured PMDI formed a network polyurea/polyuretonimine/polycarbodiimide/polyisocyanurate polymer on straw surfaces whose properties dictated the properties of strawboards. Among the different mono-, bi-, and tri-functional alcohols, amines and carboxylic acids evaluated in Part V as H-donor substitutes to moisture for reaction with PMDI on straw surfaces, ethylene glycol, resorcinol, glycerin and citric acid provided IBS values greater than the ANSI

Steam inhalation therapy: severe scalds as an adverse side effect

Science.gov (United States)

Baartmans, Martin; Kerkhof, Evelien; Vloemans, Jos; Dokter, Jan; Nijman, Susanne; Tibboel, Dick; Nieuwenhuis, Marianne

2012-01-01

Background Steam inhalation therapy is often recommended in the treatment of a common cold. However, it has no proven benefit and may in fact have serious adverse side effects in terms of burn injuries. Aim To quantify the human and economic costs of steam inhalation therapy in terms of burn injury. Design and setting A prospective database study of all patients admitted to the burn centres (Beverwijk, Groningen, Rotterdam) and the hospital emergency departments in the Netherlands. Method Number and extent of burn injuries as a result of steam inhalation therapy were analysed, as well as an approximation made of the direct costs for their medical treatment. Results Annually, on average three people are admitted to in one of the Dutch burn centres for burns resulting from steam inhalation therapy. Most victims were children, and they needed skin grafting more often than adults. The total direct medical costs for burn centre and emergency department treatment were €115 500 (£93 000), emotional costs are not reflected. Conclusion As steam inhalation therapy has no proven benefit and the number and extent of complications of this therapy in terms of burn injury are significant, especially in children, steam inhalation therapy should be considered a dangerous procedure and not recommended anymore in professional guidelines and patient brochures. PMID:22781995

Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency

DEFF Research Database (Denmark)

Reddel, Helen K.; Busse, William W.; Pedersen, Søren

2017-01-01

Background Low-dose inhaled corticosteroids (ICS) are highly effective for reducing asthma exacerbations and mortality. Conventionally, ICS treatment is recommended for patients with symptoms on more than 2 days per week, but this criterion has scant evidence. We aimed to assess the validity of t...

Influence of treatment with inhalable heroin on pulmonary function

NARCIS (Netherlands)

Buster, M. C. A.; van den Brink, W.; van Brussel, G. H. A.; van Ree, J. M.

2011-01-01

This study aims to asses the influence of inhalable heroin on pulmonary function in chronic heroin-dependent patients treated with inhalable heroin. Among 32 patients (all cigarette smokers), a spirometric test was conducted at baseline and after an average period of 10 months of treatment with

A review of the value of innovation in inhalers for COPD and asthma.

Science.gov (United States)

Virchow, Johann Christian; Akdis, Cezmi A; Darba, Josep; Dekhuijzen, Richard; Hartl, Sylvia; Kobelt, Gisela; Roger, Albert; Simoens, Steven; Toumi, Mondher; Woodhouse, Ben; Plich, Adam; Torvinen, Saku

2015-01-01

Appropriate use of inhaled therapies for asthma and chronic obstructive pulmonary disease (COPD) is critical to ensuring good patient outcomes, efficient use of healthcare resources and limiting the effects of high-morbidity. The appropriate choice of inhaler and active therapy, incorporating patient preferences, can help improve treatment adherence and long-term outcomes. Despite this, many current inhalers are non-intuitive to use, and require extensive training. In this review, an expert panel considers the evidence for the use of inhaler devices in management of COPD and asthma. The panel also evaluates the value of innovation in inhaler technologies, which optimise the use of existing molecules from a clinical, economic and societal perspective. The panel conclusion is that there remains a substantial unmet need in inhaler technology and that innovation in inhaler devices can provide real-world health benefits to patients. Furthermore, we recommend that these innovations should be supported by healthcare systems through appropriate pricing and reimbursement mechanisms.

Safety of an alkalinizing buffer designed for inhaled medications in humans.

Science.gov (United States)

Davis, Michael D; Walsh, Brian K; Dwyer, Scott T; Combs, Casey; Vehse, Nico; Paget-Brown, Alix; Pajewski, Thomas; Hunt, John F

2013-07-01

Airway acidification plays a role in disorders of the pulmonary tract. We hypothesized that the inhalation of alkalinized glycine buffer would measurably alkalinize the airways without compromising lung function or causing adverse events. We evaluated the safety of an inhaled alkaline glycine buffer in both healthy subjects and in subjects with stable obstructive airway disease. This work includes 2 open-label safety studies. The healthy controls were part of a phase 1 safety study of multiple inhalations of low-dose alkaline glycine buffer; nebulized saline was used as a comparator in 8 of the healthy controls. Subsequently, a phase 2 study in subjects with stable obstructive airway disease was completed using a single nebulized higher-dose strategy of the alkaline inhalation. We studied 20 non-smoking adults (10 healthy controls and 10 subjects with obstructive airway disease), both at baseline and after inhalation of alkaline buffer. We used spirometry and vital signs as markers of clinical safety. We used changes in fraction of exhaled nitric oxide (NO) and exhaled breath condensate (EBC) pH as surrogate markers of airway pH modification. Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital signs. Airway alkalinization was confirmed by a median increase in EBC pH of 0.235 pH units (IQR 0.56-0.03, P = .03) in subjects after inhalation of the higher-dose alkaline buffer (2.5 mL of 100 mmol/L glycine). Alkalinization of airway lining fluid is accomplished with inhalation of alkaline glycine buffer and causes no adverse effects on pulmonary function or vital signs.

Development of a physiologically based pharmacokinetic model for inhalation of jet fuels in the rat.

Science.gov (United States)

Martin, Sheppard A; Campbell, Jerry L; Tremblay, Raphael T; Fisher, Jeffrey W

2012-01-01

The pharmacokinetic behavior of the majority of jet fuel constituents has not been previously described in the framework of a physiologically based pharmacokinetic (PBPK) model for inhalation exposure. Toxic effects have been reported in multiple organ systems, though exposure methods varied across studies, utilizing either vaporized or aerosolized fuels. The purpose of this work was to assess the pharmacokinetics of aerosolized and vaporized fuels, and develop a PBPK model capable of describing both types of exposures. To support model development, n-tetradecane and n-octane exposures were conducted at 89 mg/m(3) aerosol+vapor and 1000-5000 ppm vapor, respectively. Exposures to JP-8 and S-8 were conducted at ~900-1000 mg/m(3), and ~200 mg/m(3) to a 50:50 blend of both fuels. Sub-models were developed to assess the behavior of representative constituents and grouped unquantified constituents, termed "lumps", accounting for the remaining fuel mass. The sub-models were combined into the first PBPK model for petroleum and synthetic jet fuels. Inhalation of hydrocarbon vapors was described with simple gas-exchange assumptions for uptake and exhalation. For aerosol droplets systemic uptake occurred in the thoracic region. Visceral tissues were described using perfusion and diffusion-limited equations. The model described kinetics at multiple fuel concentrations, utilizing a chemical "lumping" strategy to estimate parameters for fractions of speciated and unspeciated hydrocarbons and gauge metabolic interactions. The model more accurately simulated aromatic and lower molecular weight (MW) n-alkanes than some higher MW chemicals. Metabolic interactions were more pronounced at high (~2700-1000 mg/m(3)) concentrations. This research represents the most detailed assessment of fuel pharmacokinetics to date.

Exploring the propagation of relativistic quantum wavepackets in the trajectory-based formulation

Science.gov (United States)

Tsai, Hung-Ming; Poirier, Bill

2016-03-01

In the context of nonrelativistic quantum mechanics, Gaussian wavepacket solutions of the time-dependent Schrödinger equation provide useful physical insight. This is not the case for relativistic quantum mechanics, however, for which both the Klein-Gordon and Dirac wave equations result in strange and counterintuitive wavepacket behaviors, even for free-particle Gaussians. These behaviors include zitterbewegung and other interference effects. As a potential remedy, this paper explores a new trajectory-based formulation of quantum mechanics, in which the wavefunction plays no role [Phys. Rev. X, 4, 040002 (2014)]. Quantum states are represented as ensembles of trajectories, whose mutual interaction is the source of all quantum effects observed in nature—suggesting a “many interacting worlds” interpretation. It is shown that the relativistic generalization of the trajectory-based formulation results in well-behaved free-particle Gaussian wavepacket solutions. In particular, probability density is positive and well-localized everywhere, and its spatial integral is conserved over time—in any inertial frame. Finally, the ensemble-averaged wavepacket motion is along a straight line path through spacetime. In this manner, the pathologies of the wave-based relativistic quantum theory, as applied to wavepacket propagation, are avoided.

Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat; Etudes biocinetique et biologique comparees d'inhalations chroniques et aigues de composes uraniferes chez le rat

Energy Technology Data Exchange (ETDEWEB)

Monleau, M

2005-12-15

Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure

[INHALED ANTIBIOTICS IN TREATMENT OF NOSOCOMIAL PNEUMONIA].

Science.gov (United States)

Kuzovlev, A N; Moroz, V V; Golubev, A M

2015-01-01

Nosocomial pneumonia is the most common infection in intensive care units. Currently the problem of resistance of noso-comial pathogens to miost of antibiotics is crucial. Using of inhaled antibiotics in combination with intravenous drugs is eff ective and safe method for treatment of nosocomial pneumonia. The literature review describes current opportunities of ihhaled antibiotic therapy of nosocomial pneumonia, descriptions of drugs, the advantages and disadvantages of this treatment. Special attention is paid for using inhaled aminoglycosides for nosocomial pneumonia.

Improved Formulations for Air-Surface Exchanges Related to National Security Needs: Dry Deposition Models

Energy Technology Data Exchange (ETDEWEB)

Droppo, James G.

2006-07-01

The Department of Homeland Security and others rely on results from atmospheric dispersion models for threat evaluation, event management, and post-event analyses. The ability to simulate dry deposition rates is a crucial part of our emergency preparedness capabilities. Deposited materials pose potential hazards from radioactive shine, inhalation, and ingestion pathways. A reliable characterization of these potential exposures is critical for management and mitigation of these hazards. A review of the current status of dry deposition formulations used in these atmospheric dispersion models was conducted. The formulations for dry deposition of particulate materials from am event such as a radiological attack involving a Radiological Detonation Device (RDD) is considered. The results of this effort are applicable to current emergency preparedness capabilities such as are deployed in the Interagency Modeling and Atmospheric Assessment Center (IMAAC), other similar national/regional emergency response systems, and standalone emergency response models. The review concludes that dry deposition formulations need to consider the full range of particle sizes including: 1) the accumulation mode range (0.1 to 1 micron diameter) and its minimum in deposition velocity, 2) smaller particles (less than .01 micron diameter) deposited mainly by molecular diffusion, 3) 10 to 50 micron diameter particles deposited mainly by impaction and gravitational settling, and 4) larger particles (greater than 100 micron diameter) deposited mainly by gravitational settling. The effects of the local turbulence intensity, particle characteristics, and surface element properties must also be addressed in the formulations. Specific areas for improvements in the dry deposition formulations are 1) capability of simulating near-field dry deposition patterns, 2) capability of addressing the full range of potential particle properties, 3) incorporation of particle surface retention/rebound processes, and

Functional testing of an inhalable nanoparticle based influenza vaccine using a human precision cut lung slice technique.

Directory of Open Access Journals (Sweden)

Vanessa Neuhaus

Full Text Available Annual outbreaks of influenza infections, caused by new influenza virus subtypes and high incidences of zoonosis, make seasonal influenza one of the most unpredictable and serious health threats worldwide. Currently available vaccines, though the main prevention strategy, can neither efficiently be adapted to new circulating virus subtypes nor provide high amounts to meet the global demand fast enough. New influenza vaccines quickly adapted to current virus strains are needed. In the present study we investigated the local toxicity and capacity of a new inhalable influenza vaccine to induce an antigen-specific recall response at the site of virus entry in human precision-cut lung slices (PCLS. This new vaccine combines recombinant H1N1 influenza hemagglutinin (HAC1, produced in tobacco plants, and a silica nanoparticle (NP-based drug delivery system. We found no local cellular toxicity of the vaccine within applicable concentrations. However higher concentrations of NP (≥10(3 µg/ml dose-dependently decreased viability of human PCLS. Furthermore NP, not the protein, provoked a dose-dependent induction of TNF-α and IL-1β, indicating adjuvant properties of silica. In contrast, we found an antigen-specific induction of the T cell proliferation and differentiation cytokine, IL-2, compared to baseline level (152±49 pg/mg vs. 22±5 pg/mg, which could not be seen for the NP alone. Additionally, treatment with 10 µg/ml HAC1 caused a 6-times higher secretion of IFN-γ compared to baseline (602±307 pg/mg vs. 97±51 pg/mg. This antigen-induced IFN-γ secretion was further boosted by the adjuvant effect of silica NP for the formulated vaccine to a 12-fold increase (97±51 pg/mg vs. 1226±535 pg/mg. Thus we were able to show that the plant-produced vaccine induced an adequate innate immune response and re-activated an established antigen-specific T cell response within a non-toxic range in human PCLS at the site of virus entry.

Inhalational and dermal exposures during spray application of biocides.

Science.gov (United States)

Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

2005-01-01

Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a

Evaluation of Inhaler Techniques Among Asthma Patients Seen in ...

African Journals Online (AJOL)

Background: An Adequate and an effective dose of inhalation drugs can be administered only if the correct inhaler‑specific technique is followed by asthma patients. There is paucity of data on this subject among Nigerians and Africans. Aims: This observational study was to assess the inhaler techniques among asthma ...

Experimental study of inhalation injury

International Nuclear Information System (INIS)

Hamamoto, Junji; Ohura, Takehiko; Yoshida, Tetsunori; Ono, Ichiro; Iida, Kazunori; Ooiwa, Akira

1984-01-01

We conducted the following inhalation injury experiment on dogs. A hose was connected to the chimney of a stove so that wood smoke could be led to the dog by means of damper adjustment. Under intravenous anesthesia, the dog was intubated and made to inhale the wood smoke for from 5 to 10 minutes at a smoke temperature of between 55 and 60 C. After this inhalation, observation of trachea by a fiberoptic bronchoscopy was done and blood gas change, blood analysis, serum electrolytes and cardiac output were observed with a passage of time. Furthermore, we did lung scan using 133xe and performed autopsies. We injected 0.3 microcurie of 133Xe per 1 kg body weight in its vein of the dog's foreleg. The concentration in the lung reached maximum 20 seconds after the injection and then washed out with expiration. In the control experiment with a normal dog, it was almost all washed out 70 seconds after the 133Xe injection. But the delay of wash out time was observed in smoke inhaled dogs. In other words it can be said that the wash out time was dependent on the degree of injury. When these data were processed by a computer, and exponential approximation decay curve was obtained. Then these data were replotted into semi-logarithmic chart and a linear line was obtained. One may interprete the clearance rate recorded on the graph as the ability of the lung to wash out 133Xe, that is, the degree of injury of the lung. The clearance rate had a tendancy to concentrate between 3.5 to 5.0 when observed 2 to 7 hours after the injury. However when observed 20 to 27 hours, concentration was between 2.4 to 3.2. Furthermore, the clearance rate for each lung regions were obtained and compared with one another by means of proper computer program. The clearance rate had lower values at lower region of lung, that is, deterioration of lung function was greater. (J.P.N.)

Inhalation Toxicology Research Institute. Annual report, October 1, 1981-September 30, 1982

International Nuclear Information System (INIS)

Snipes, M.B.; Marshall, T.C.; Martinez, B.S.

1982-12-01

Studies are presented of the effect on man of airborne particulates and gaseous emissions associated with the production of energy. Included in the report from the Inhalation Toxicology Research Institute are papers on: (1) the physical and chemical characterization of energy technology aerosols; (2) laboratory studies of aerosol generation and characterization; (3) in vitro predictors of toxicity; (4) disposition and fate of inhaled materials; (5) dose-response relationships for inhaled radionuclides; (6) dose-response relationships for inhaled chemical toxicants; (7) biological factors which influence dose-response relationships; and (8) risk assessment

Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children.

LENUS (Irish Health Repository)

Ni Chroinin, Muireann

2009-01-01

Consensus statements recommend the addition of long-acting inhaled ss2-agonists (LABA) only in asthmatic patients who are inadequately controlled on inhaled corticosteroids (ICS). It is not uncommon for some patients to be commenced on ICS and LABA together as initial therapy.

Inhaled Corticosteroids (ICSs) and Pregnancy

Science.gov (United States)

... of the airways in the lungs and reduce mucus production so that asthma attacks are less likely. ... of medicine that would be in the breast milk following inhalation is likely too small to cause ...

Bronchospasm and anaphylactic shock following lidocaine aerosol inhalation in a patient with butane inhalation lung injury.

Science.gov (United States)

Lee, Min-Young; Park, Kyong Ah; Yeo, So-Jeong; Kim, Shin-Hee; Goong, Hyeun-Jeong; Jang, An-Soo; Park, Choon-Sik

2011-10-01

Allergic reactions to local anesthetics are very rare and represent inhalation lung injury due to butane gas fuel. On the fifth day, he developed an asthmatic attack and anaphylactic shock immediately after lidocaine aerosol administration to prepare for bronchoscopy to confirm an acute inhalational lung injury diagnosis. Cardiopulmonary resuscitation was performed immediately after respiratory arrest, and the patient was admitted to the intensive care unit intubated and on a ventilator. He was extubated safely on the third post-cardiopulmonary resuscitation day. These observations suggest that aerosol lidocaine anesthesia may cause airway narrowing and anaphylactic shock. Practitioners should be aware of this potential complication. We report on this case with a brief review of the literature.

Inhaled Antibiotics for Ventilator-Associated Infections.

Science.gov (United States)

Palmer, Lucy B

2017-09-01

Multidrug-resistant organisms are creating a challenge for physicians treating the critically ill. As new antibiotics lag behind the emergence of worsening resistance, intensivists in countries with high rates of extensively drug-resistant bacteria are turning to inhaled antibiotics as adjunctive therapy. These drugs can provide high concentrations of drug in the lung that could not be achieved with intravenous antibiotics without significant systemic toxicity. This article summarizes current evidence describing the use of inhaled antibiotics for the treatment of bacterial ventilator-associated pneumonia and ventilator-associated tracheobronchitis. Preliminary data suggest aerosolized antimicrobials may effectively treat resistant pathogens with high minimum inhibitory concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhaled mycotoxins lead to acute renal failure.

Science.gov (United States)

Di Paolo, N; Guarnieri, A; Garosi, G; Sacchi, G; Mangiarotti, A M; Di Paolo, M

1994-01-01

Mysterious deaths of archeologists after opening Egyptian tombs have been suspected, but never proved, to be secondary to inhalation of mycotoxin. We observed a case of acute renal failure (ARF) due to inhalation of ochratoxin A produced by a mould of the species Aspergillus ochraceus. After working 8 h in a granary closed for several months, a farmer and his wife suffered respiratory distress; the woman developed non-oliguric ARF and biopsy revealed tubulonecrosis. A strain of Aspergillus ochraceus producing ochratoxin was isolated from the wheat.

High-Level Waste Glass Formulation Model Sensitivity Study 2009 Glass Formulation Model Versus 1996 Glass Formulation Model

International Nuclear Information System (INIS)

Belsher, J.D.; Meinert, F.L.

2009-01-01

This document presents the differences between two HLW glass formulation models (GFM): The 1996 GFM and 2009 GFM. A glass formulation model is a collection of glass property correlations and associated limits, as well as model validity and solubility constraints; it uses the pretreated HLW feed composition to predict the amount and composition of glass forming additives necessary to produce acceptable HLW glass. The 2009 GFM presented in this report was constructed as a nonlinear optimization calculation based on updated glass property data and solubility limits described in PNNL-18501 (2009). Key mission drivers such as the total mass of HLW glass and waste oxide loading are compared between the two glass formulation models. In addition, a sensitivity study was performed within the 2009 GFM to determine the effect of relaxing various constraints on the predicted mass of the HLW glass.

Risk based In Vitro Performance Assessment of Extended Release Abuse Deterrent Formulations

Science.gov (United States)

Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N.; Khan, Mansoor A.

2016-01-01

High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products. PMID:26784976

Inhalation Toxicology Research Institute annual report, October 1, 1982-September 30, 1983

International Nuclear Information System (INIS)

1983-12-01

The mission of the Inhalation Toxicology Research Institute (ITRI) is to investigate the nature and magnitude of human health effects that might result from inhalation of airborne materials encountered in the work place, special attention is directed toward airborne particulate and gaseous emissions released by various energy technologies or from national defense activities. Included are five papers on the physical and chemical characterization of energy technology aerosols, 10 papers on laboratory studies of aerosol generation and characterization, 11 papers on in vitro predictors of toxicity, 12 papers on disposition and fate of inhaled materials, 24 papers on dose-response relationships for inhaled radionuclides, 3 papers on dose-response relationships for inhaled chemical toxicants, 8 papers on biological factors that influence dose-response relationships, and 4 papers are concerned with risk assessment

Exposures from external radiation and from inhalation of resuspended material

International Nuclear Information System (INIS)

Jacob, P.; Roth, P.; Golikov, V.; Balonov, M.; Erkin, V.; Likhtariov, I.; Garger, E.; Kashparov, V.

1996-01-01

In the modelling of external exposures due to cesium released during the reactor accident of Chernobyl, gamma dose rates in air over open undisturbed sites are considered to be different according to the unsoluble fraction in the deposit. This is taken into account by forming different classes according to the distance from the Chernobyl NPP. The effect of the different migration behavior in these distance classes on the gamma dose rate in air is found to increase with time. Predictions of gamma dose rates in air are based on measurements of the nuclear weapons tests fallout. Various population groups in the CIS countries are defined according to their place of residence (rural or urban), their occupation or age (indoor resp. outdoor workers, pensioners, school-children, or preschool-children), and their kind of residence (wooden, brick, or multi-storey house). Model results for various population groups are compared with the results of TLD-measurements of individual external exposures. For the calculation of inhalation doses, the new ICRP model for the respiratory tract was used. The dose assessments were conducted for measured size resolved activity distributions of resuspended material, obtained at different locations and for several kinds of agricultural operations. Inhalation doses vary considerably with respect to different kinds of work. Tractor drivers receive much higher doses than other agricultural workers, especially when the cabin window of the tractor is open. Effective doses due to the inhalation of resuspended plutonium are assessed to be a few μSv per initial deposit of one kBq/m 2 . Inhalation doses from 137 Cs are usually smaller by an order of magnitude than the doses from Pu, provided a high solubility is assumed for resuspended Cs

Development of controlled release formulations of azadirachtin-A employing poly(ethylene glycol) based amphiphilic copolymers.

Science.gov (United States)

Kumar, Jitendra; Shakil, Najam A; Singh, Manish K; Singh, Mukesh K; Pandey, Alka; Pandey, Ravi P

2010-05-01

Controlled release (CR) formulations of azadirachtin-A, a bioactive constituent derived from the seed of Azadirachta indica A. Juss (Meliaceae), have been prepared using commercially available polyvinyl chloride, polyethylene glycol (PEG) and laboratory synthesized poly ethylene glycol-based amphiphilic copolymers. Copolymers of polyethylene glycol and various dimethyl esters, which self assemble into nano micellar aggregates in aqueous media, have been synthesized. The kinetics of azadirachtin-A, release in water from the different formulations was studied. Release from the commercial polyethylene glycol (PEG) formulation was faster than the other CR formulations. The rate of release of encapsulated azadirachtin-A from nano micellar aggregates is reduced by increasing the molecular weight of PEG. The diffusion exponent (n value) of azadirachtin-A, in water ranged from 0.47 to 1.18 in the tested formulations. The release was diffusion controlled with a half release time (t(1/2)) of 3.05 to 42.80 days in water from different matrices. The results suggest that depending upon the polymer matrix used, the application rate of azadirachtin-A can be optimized to achieve insect control at the desired level and period.

Opinion of pneumologists on the importance of inhalers in patients with asthma or COPD

Directory of Open Access Journals (Sweden)

Mitja Košnik

2017-04-01

Full Text Available Background: Medications for asthma and COPD are mainly used in the form of inhalations. A survey was performed to obtain the opinion of experts about the importance of inhalers in inhaled drug therapy.Methods: All members–pulmonologists of the Slovenian Respiratory Society were invited to participate in the survey using a two-stage Delphi method. The result of each response were shown by the median and interquartile range, whereby we calculated the level of consensus.Results: 176 doctors were invited. Most questions were answered by 49 (27.8 % participants. In the second round 42 doctors responded. As many as 33 out of 41 respondents (80.5 % felt that in the treatment of asthma and COPD the selection of medicines and inhalers are equally important. When choosing an inhaler, it is crucial that it is simple to instruct the patients about its use. Respondents highly agreed with the statement that patients should receive a prescription for inhaler only after they have been trained on how to use it. As appropriate persons for the training of patients on the use of inhalers the respondents recognized (from most to least suitable pulmonologists, nurses, general practitioners or pharmacists. 53.8 % of respondents considered that the patient’s skill of the use of inhaler should be checked on every visit to the doctor. Respondents believed that replacing inhalers without consulting the treating doctor may result in incorrect use of the inhaler, poor patient compliance, more exacerbations of the disease and poorer disease control. Some consensus with an indifferent median of 4.5 was reached with regard to the argument that the doctor should prescribe the inhaler that is the cheapest for society.Conclusions: Slovenian pulmonologists believe that any change of inhaler is a critical event, which must be coordinated with the patient and the doctor.

Immediate and long-term effects of polysaccharides-based formulations on human skin

Directory of Open Access Journals (Sweden)

Flavio Bueno de Camargo Junior

2012-09-01

Full Text Available A new trend in cosmetic formulations is the use of biotechnological raw materials as the polysaccharides from Klebsiella pneumoniae, which are supposed to enhance cell renewal, improve skin hydration and micro-relief. Botanical extracts of Myrtus communis leaves contain different sugars, which may provide the same benefits. Thus, the objective of this study was to evaluate through objective and subjective analysis the immediate and long-term effects of cosmetic formulations containing polysaccharides biotechnologically-originated and / or the ones contained in Myrtus communis extracts. Three polysaccharide-based and placebo formulations were applied on the forearm skin of 40 volunteers. Skin hydration, transepidermal water loss (TEWL, viscoelasticity and skin micro-relief measurements were made before and 2 hours after a single application and after 15 and 30 day-periods of daily applications. Answers to a questionnaire about perceptions of formulation cosmetic features constituted the subjective analysis. All polysaccharide-based formulations enhanced skin hydration. Formulations with isolated or combined active substances improved skin barrier function as compared to placebo, in the short and long term studies. Formulations containing Myrtus communis extracts had the highest acceptance. Results suggest that daily use of formulations containing these substances is important for protection of the skin barrier function.Uma nova tendência em formulações cosméticas é a utilização de matérias-primas biotecnológicas como os polissacarídeos de Klebsiella pneumoniae, que pode aumentar a renovação celular e melhor a hidratação e micro-relevo da pele. Por outro lado, o extrato vegetal de Myrtus communis contém diferentes polissacarídeos, que também podem proporcionar benefícios à pele. Assim, o objetivo do estudo foi a avaliação dos efeitos imediatos e em longo prazo, de formulações cosméticas contendo polissacarídeos obtidos por

[Efficacy of a new fenbendazole formulation produced by nanotechnology-based drug delivery system against nematodosis].

Science.gov (United States)

Varlamova, A I; Arkhipov, I A; Odoevskaia, I M; Danilevskaia, N V; Khalikov, S S; Chistiachenko, Iu S; Dushkin, A V

2014-01-01

The efficacy of a new fenbendazile formulation produced by nanotechnology-based drug delivery system was investigated in45 sheep naturally infected with gastrointestinal nematodes. The formulation showed 95.6% efficacy against Nematodes spp. at a dose of 1.0 mg/kg dw of its active ingredient and 100% efficacy against other species of gastrointestinal nematodes. Given at a dose of 10 mg/kg dw, the basic drug--fenbendazole (substance) displayed 96.39 and 100% efficacy, respectively.

Inhalation device options for the management of chronic obstructive pulmonary disease.

Science.gov (United States)

DePietro, Michael; Gilbert, Ileen; Millette, Lauren A; Riebe, Michael

2018-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by chronic respiratory symptoms and airflow limitation, resulting from abnormalities in the airway and/or damage to the alveoli. Primary care physicians manage the healthcare of a large proportion of patients with COPD. In addition to determining the most appropriate medication regimen, which usually includes inhaled bronchodilators with or without inhaled corticosteroids, physicians are charged with optimizing inhalation device selection to facilitate effective drug delivery and patient adherence. The large variety of inhalation devices currently available present numerous challenges for physicians that include: (1) gaining knowledge of and proficiency with operating different device classes; (2) identifying the most appropriate inhalation device for the patient; and (3) providing the necessary education and training for patients on device use. This review provides an overview of the inhalation device types currently available in the United States for delivery of COPD medications, including information on their successful operation and respective advantages and disadvantages, factors to consider in matching a device to an individual patient, the need for device training for patients and physicians, and guidance for improving treatment adherence. Finally, the review will discuss established and novel tools and technology that may aid physicians in improving education and promoting better adherence to therapy.

Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke.

Science.gov (United States)

Wang, Hailian; Li, Peiying; Xu, Na; Zhu, Ling; Cai, Mengfei; Yu, Weifeng; Gao, Yanqin

2016-01-01

Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms.

Formulation Optimization and Ex Vivo and In Vivo Evaluation of Celecoxib Microemulsion-Based Gel for Transdermal Delivery.

Science.gov (United States)

Cao, Mengyuan; Ren, Lili; Chen, Guoguang

2017-08-01

Celecoxib (CXB) is a poorly aqueous solubility sulfonamide non-steroidal anti-inflammatory drug (NSAID). Hence, the formulation of CXB was selected for solubilization and bioavailability. To find out suitable formulation for microemulsion, the solubility of CXB in triacetin (oil phase), Tween 80 (surfactant), and Transcutol-P (co-surfactant) was screened respectively and optimized by using orthogonal experimental design. The Km value and concentration of oil, S mix , and water were confirmed by pseudo-ternary phase diagram studies and central composite design. One percent carbopol 934 was added to form CXB microemulsion-based gel. The final formulation was evaluated for its appearance, pH, viscosity, stability, drug content determination, globule size, and zeta potential. Its ex vivo drug permeation and the in vivo pharmacokinetic was investigated. Further research was performed to ensure the safety and validity by skin irritation study and in vivo anti-inflammatory activity study. Ex vivo permeation study in mice was designed to compare permeation and transdermal ability between microemulsion formulation and conventional gel. The results revealed that optimized microemulsion-based gel gained higher permeation based on smaller globule size and high drug loading of microemulsion. Transdermal ability was also greatly improved. Bioavailability was compared to market Celebrex® by the in vivo pharmacokinetic study in rabbits. The results indicated that CXB microemulsion-based gel had better bioavailability than Celebrex®.

Aerosol lung inhalation scintigraphy in normal subjects

Energy Technology Data Exchange (ETDEWEB)

Sui, Osamu; Shimazu, Hideki

1985-03-01

We previously reported basic and clinical evaluation of aerosol lung inhalation scintigraphy with /sup 99m/Tc-millimicrosphere albumin (milli MISA) and concluded aerosol inhalation scintigraphy with /sup 99m/Tc-milli MISA was useful for routine examination. But central airway deposit of aerosol particles was found in not only the patients with chronic obstructive pulmonary disease (COPD) but also normal subjects. So we performed aerosol inhalation scintigraphy in normal subjects and evaluated their scintigrams. The subjects had normal values of FEVsub(1.0)% (more than 70%) in lung function tests, no abnormal findings in chest X-ray films and no symptoms and signs. The findings of aerosol inhalation scintigrams in them were classified into 3 patterns; type I: homogeneous distribution without central airway deposit, type II: homogeneous distribution with central airway deposit, type III: inhomogeneous distribution. These patterns were compared with lung function tests. There was no significant correlation between type I and type II in lung function tests. Type III was different from type I and type II in inhomogeneous distribution. This finding showed no correlation with %VC, FEVsub(1.0)%, MMF, V radical50 and V radical50/V radical25, but good correlation with V radical25 in a maximum forced expiratory flow-volume curve. Flow-volume curve is one of the sensitive methods in early detection of COPD, so inhomogeneous distribution of type III is considered to be due to small airway dysfunction.

Oral versus inhaled antibiotics for bronchiectasis.

Science.gov (United States)

Spencer, Sally; Felix, Lambert M; Milan, Stephen J; Normansell, Rebecca; Goeminne, Pieter C; Chalmers, James D; Donovan, Tim

2018-03-27

Bronchiectasis is a chronic inflammatory disease characterised by a recurrent cycle of respiratory bacterial infections associated with cough, sputum production and impaired quality of life. Antibiotics are the main therapeutic option for managing bronchiectasis exacerbations. Evidence suggests that inhaled antibiotics may be associated with more effective eradication of infective organisms and a lower risk of developing antibiotic resistance when compared with orally administered antibiotics. However, it is currently unclear whether antibiotics are more effective when administered orally or by inhalation. To determine the comparative efficacy and safety of oral versus inhaled antibiotics in the treatment of adults and children with bronchiectasis. We identified studies through searches of the Cochrane Airways Group's Specialised Register (CAGR), which is maintained by the Information Specialist for the group. The Register contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched ClinicalTrials.gov and the WHO trials portal. We searched all databases in March 2018 and imposed no restrictions on language of publication. We planned to include studies which compared oral antibiotics with inhaled antibiotics. We would have considered short-term use (less than four weeks) for treating acute exacerbations separately from longer-term use as a prophylactic (4 weeks or more). We would have considered both intraclass and interclass comparisons. We planned to exclude studies if the participants received continuous or high-dose antibiotics immediately before the start of the trial, or if they have received a diagnosis of cystic fibrosis (CF), sarcoidosis, active allergic bronchopulmonary aspergillosis or active non-tuberculous Mycobacterial infection

Particle exposure and inhaled dose during commuting in Singapore

Science.gov (United States)

Tan, Sok Huang; Roth, Matthias; Velasco, Erik

2017-12-01

Exposure concentration and inhaled dose of particles during door-to-door trips walking and using motorized transport modes (subway, bus, taxi) are evaluated along a selected route in a commercial district of Singapore. Concentrations of particles smaller than 2.5 μm in size (PM2.5), black carbon, particle-bound polycyclic aromatic hydrocarbons, number of particles, active surface area and carbon monoxide have been measured in-situ using portable instruments. Simultaneous measurements were conducted at a nearby park to capture the background concentrations. The heart rate of the participants was monitored during the measurements as a proxy of the inhalation rate used to calculate the inhaled dose of particles. All measured metrics were highest and well above background levels during walking. No significant difference was observed in the exposure concentration of PM2.5 for the three motorized transport modes, unlike for the metrics associated with ultrafine particles (UFP). The concentration of these freshly emitted particles was significantly lower on subway trips. The absence of combustion sources, use of air conditioning and screen doors at station platforms are effective measures to protect passengers' health. For other transport modes, sections of trips close to accelerating and idling vehicles, such as bus stops, traffic junctions and taxi stands, represent hotspots of particles. Reducing the waiting time at such locations will lower pollutants exposure and inhaled dose during a commute. After taking into account the effect of inhalation and travel duration when calculating dose, the health benefit of commuting by subway for this particular district of Singapore became even more evident. For example, pedestrians breathe in 2.6 and 3.2 times more PM2.5 and UFP, respectively than subway commuters. Public buses were the second best alternative. Walking emerged as the worst commuting mode in terms of particle exposure and inhaled dose.

The fate of inhaled antibiotics after deposition in cystic fibrosis: How to get drug to the bug?

Science.gov (United States)

Bos, Aukje C; Passé, Kimberly M; Mouton, Johan W; Janssens, Hettie M; Tiddens, Harm A W M

2017-01-01

Chronic airway infections in patients with cystic fibrosis (CF) are most often treated with inhaled antibiotics of which deposition patterns have been extensively studied. However, the journey of aerosol particles does not end after deposition within the bronchial tree. To review how local conditions affect the clinical efficacy of antibiotic aerosol particles after deposition in the airways of patients with CF. Electronic databases were searched from inception to September 2015. Original studies describing the effect of CF sputum or bacterial factors on antibiotic efficacy and formulations to increase efficacy were included. 35 articles were included which mostly described in vitro studies and mainly investigated aminoglycosides. After deposition, diffusion through the mucus layer was reduced for aminoglycosides, β-lactam antibiotics and fluoroquinolones. Within CF mucus, low oxygen tension adversely affected aminoglycosides, β-lactam antibiotics, and chloramphenicol; and molecules inactivated aminoglycosides but not β-lactam antibiotics. Finally, the alginate layer surrounding Pseudomonas aeruginosa was an important factor in the resistance against all antibiotics. After deposition in the airways, the local efficacy of inhaled antibiotics can be reduced by molecules within CF mucus and the alginate layer surrounding P. aeruginosa. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Unintended inhalation of nitric oxide by contamination of compressed air: physiologic effects and interference with intended nitric oxide inhalation in acute lung injury.

Science.gov (United States)

Benzing, A; Loop, T; Mols, G; Geiger, K

1999-10-01

Compressed air from a hospital's central gas supply may contain nitric oxide as a result of air pollution. Inhaled nitric oxide may increase arterial oxygen tension and decrease pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. Therefore, the authors wanted to determine whether unintentional nitric oxide inhalation by contamination of compressed air influences arterial oxygen tension and pulmonary vascular resistance and interferes with the therapeutic use of nitric oxide. Nitric oxide concentrations in the compressed air of a university hospital were measured continuously by chemiluminescence during two periods (4 and 2 weeks). The effects of unintended nitric oxide inhalation on arterial oxygen tension (n = 15) and on pulmonary vascular resistance (n = 9) were measured in patients with acute lung injury and acute respiratory distress syndrome by changing the source of compressed air of the ventilator from the hospital's central gas supply to a nitric oxide-free gas tank containing compressed air. In five of these patients, the effects of an additional inhalation of 5 ppm nitric oxide were evaluated. During working days, compressed air of the hospital's central gas supply contained clinically effective nitric oxide concentrations (> 80 parts per billion) during 40% of the time. Change to gas tank-supplied nitric oxide-free compressed air decreased the arterial oxygen tension by 10% and increased pulmonary vascular resistance by 13%. The addition of 5 ppm nitric oxide had a minimal effect on arterial oxygen tension and pulmonary vascular resistance when added to hospital-supplied compressed air but improved both when added to tank-supplied compressed air. Unintended inhalation of nitric oxide increases arterial oxygen tension and decreases pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. The unintended nitric oxide inhalation interferes with the

Real-time measurement of inhaled and exhaled cigarette smoke: Implications for dose

Energy Technology Data Exchange (ETDEWEB)

McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John, E-mail: conor_mcgrath@bat.co [British American Tobacco, Group R and D Centre, Southampton, SO15 8TL (United Kingdom)

2009-02-01

Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of 150 -- 250 nm count median diameter (CMD). Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, the average CMD of inhaled smoke was 160 nm while the average CMD of exhaled smoke was 239 nm with an average growth factor of 1.5.

Real-time measurement of inhaled and exhaled cigarette smoke: Implications for dose

International Nuclear Information System (INIS)

McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John

2009-01-01

Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of 150 -- 250 nm count median diameter (CMD). Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, the average CMD of inhaled smoke was 160 nm while the average CMD of exhaled smoke was 239 nm with an average growth factor of 1.5.

Computer tomographic assessment of partial liquid ventilation in dogs with inhalation injury

International Nuclear Information System (INIS)

Wang Liya; Gong Honghan; Xiao Xiangzuo; Guo Guanghua; Li Guohui; Zhou Li; Fu Lihui; Fan Kunwu

2004-01-01

Objective: To analyze CT and pathologic findings of lung in dogs with inhalation injury, and to provide reliable basis to explore the mechanism of partial liquid ventilation (PLV) treatment on inhalation injury. Methods: Respiratory tract injury models in 14 dogs were made by steam inhalation and they were divided into 2 groups. The control group was treated by high frequency ventilation (HFV) and the treatment group was treated by partial liquid with perfluorocarbon plus HFV. CT scan of the lung in dogs with inhalation injury was performed before and after perfluorocarbon (PFC) PLV, and then the histopathologic pieces with isolation lung were obtained. Analysis and comparison of the results among them was conducted. Results: After steam inhalation injury, CT appeared as exudation with patchy and mass in 6 dogs, cotton-wool spots in 2 dogs, ground-glass opacity in 2 dogs, and consolidation in 4 dogs. CT appeared as mass in 5 dogs with inhalation injury of perfluorocarbon-filled lungs during partial liquid ventilation, patchy in 2 dogs, and homogeneous in 1 dog. The distribution of perfluorocarbon was in the posterior region of lung. The CT findings were in accordance with those in histopathology. Conclusion: Perfluorocarbon is distributed predominantly in the dependent regions of the lung and the distribution of perfluorocarbon is gravity dependent. It is benefit for the inhalation injury

Pentoxifylline does not alter the response to inhaled grain dust.

Science.gov (United States)

Jagielo, P J; Watt, J L; Quinn, T J; Knapp, H R; Schwartz, D A

1997-05-01

Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophil sequestration in the lung and inhibit endotoxin-mediated release of tumor necrosis factor-alpha (TNF-alpha). Previously, we have shown that endotoxin appears to be the principal agent in grain dust causing airway inflammation and airflow obstruction following grain dust inhalation. To determine whether PTX affects the physiologic and inflammatory events following acute grain dust inhalation, 10 healthy, nonsmoking subjects with normal airway reactivity were treated with PTX or placebo (PL) followed by corn dust extract (CDE) inhalation (0.08 mL/kg), using a single-blinded, crossover design. Subjects received PTX (1,200 mg/d) or PL for 4 days prior to CDE inhalation and 400 mg PTX or PL on the exposure day. Both respiratory symptoms and declines in FEV1 and FVC occurred following CDE exposure in both groups, but there were no significant differences in the frequency of symptoms or percent declines from baseline in the FEV1 and FVC at any of the time points measured in the study. Elevations in peripheral blood leukocyte and neutrophil concentrations and BAL total cell, neutrophil, TNF-alpha, and interleukin-8 concentrations were measured 4 h following exposure to CDE in both the PTX- and PL-treated subjects, but no significant differences were found between treatment groups. These results suggest that pretreatment with PTX prior to inhalation of CDE, in the doses used in this study, does not alter the acute physiologic or inflammatory events following exposure to inhaled CDE.

Methanol toxicity secondary to inhalant abuse in adult men.

Science.gov (United States)

Wallace, Erik A; Green, Adam S

2009-03-01

The purpose of this report is to evaluate the presentation, treatment, and outcomes of adults with methanol toxicity from inhalation of carburetor cleaning fluid fumes. Retrospective chart review of adults with positive serum volatile screen for methanol and history of carburetor cleaning fluid fume inhalation. Sixteen patients were admitted 68 times. Eleven Native American patients accounted for 90% of admissions. Sixty-five cases presented with nausea/vomiting; 27 with intoxication or altered mental status; 21 with specific visual complaints. About 93% had a pH or=10 mOsm/L, and 69% had anion gap >16. Ten had an initial serum methanol level or=50 mg/dL. Six patients had a measurable serum ethanol level. Of the 29 patients with a methanol level of 20-49 mg/dL, 20 received intravenous antidote (ethanol or fomepizole); three received an antidote and hemodialysis. All who presented with a serum methanol level >or=50 mg/dL received intravenous ethanol or fomepizole. All visual symptoms resolved before discharge and all patients survived without sequelae. Discussion. This is the largest reported number of cases of methanol toxicity from the inhalation of carburetor cleaning fluid fumes and demonstrates a problem with recurrent abuse among some older Native American men. Intentional inhalation of methanol fumes may produce toxicity. Clinicians need to question patients, especially older Native American men, regarding the possible inhalation of carburetor cleaning fluid fumes in those who present with an unexplained metabolic anion gap acidosis.

Socioeconomic inequalities in adherence to inhaled maintenance medications and clinical prognosis of COPD

DEFF Research Database (Denmark)

Tøttenborg, Sandra Søgaard; Lange, Peter; Johnsen, Søren Paaske

2016-01-01

BACKGROUND: Low socioeconomic status has been associated with adverse outcomes in chronic obstructive pulmonary disease (COPD), but population-based data are sparse. We examined the impact of education, employment, income, ethnicity, and cohabitation on the risk of suboptimal adherence to inhaled...

Inhaled plutonium oxide in dogs

International Nuclear Information System (INIS)

Park, J.F.

1982-01-01

This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for lifespan dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary-fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12μCi. Nineteen of the dogs exposed to 238 Pu haved died during the first 7-1/2 yr after exposure due to bone and/or lung tumors; their body burdens at death ranged from 0.7 to 10μCi. Chronic lymphopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2

Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black.

Science.gov (United States)

Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Küttler, Karin; Wohlleben, Wendel; Hofmann, Thomas; Gröters, Sibylle; Wiench, Karin; van Ravenzwaay, Bennard; Landsiedel, Robert

2013-06-17

Carbon nanotubes, graphene, graphite nanoplatelets and carbon black are seemingly chemically identical carbon-based nano-materials with broad technological applications. Carbon nanotubes and carbon black possess different inhalation toxicities, whereas little is known about graphene and graphite nanoplatelets. In order to compare the inhalation toxicity of the mentioned carbon-based nanomaterials, male Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 hours per day on 5 consecutive days. Target concentrations were 0.1, 0.5, or 2.5 mg/m3 for multi-wall carbon nanotubes and 0.5, 2.5, or 10 mg/m3 for graphene, graphite nanoplatelets and low-surface carbon black. Toxicity was determined after end of exposure and after three-week recovery using broncho-alveolar lavage fluid and microscopic examinations of the entire respiratory tract. No adverse effects were observed after inhalation exposure to 10 mg/m3 graphite nanoplatelets or relatively low specific surface area carbon black. Increases of lavage markers indicative for inflammatory processes started at exposure concentration of 0.5 mg/m3 for multi-wall carbon nanotubes and 10 mg/m3 for graphene. Consistent with the changes in lavage fluid, microgranulomas were observed at 2.5 mg/m3 multi-wall carbon nanotubes and 10 mg/m3 graphene. In order to evaluate volumetric loading of the lung as the key parameter driving the toxicity, deposited particle volume was calculated, taking into account different methods to determine the agglomerate density. However, the calculated volumetric load did not correlate to the toxicity, nor did the particle surface burden of the lung. The inhalation toxicity of the investigated carbon-based materials is likely to be a complex interaction of several parameters. Until the properties which govern the toxicity are identified, testing by short-term inhalation is the best option to identify hazardous properties in order to avoid unsafe applications or select

Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black

Science.gov (United States)

2013-01-01

Background Carbon nanotubes, graphene, graphite nanoplatelets and carbon black are seemingly chemically identical carbon-based nano-materials with broad technological applications. Carbon nanotubes and carbon black possess different inhalation toxicities, whereas little is known about graphene and graphite nanoplatelets. Methods In order to compare the inhalation toxicity of the mentioned carbon-based nanomaterials, male Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 hours per day on 5 consecutive days. Target concentrations were 0.1, 0.5, or 2.5 mg/m3 for multi-wall carbon nanotubes and 0.5, 2.5, or 10 mg/m3 for graphene, graphite nanoplatelets and low-surface carbon black. Toxicity was determined after end of exposure and after three-week recovery using broncho-alveolar lavage fluid and microscopic examinations of the entire respiratory tract. Results No adverse effects were observed after inhalation exposure to 10 mg/m3 graphite nanoplatelets or relatively low specific surface area carbon black. Increases of lavage markers indicative for inflammatory processes started at exposure concentration of 0.5 mg/m3 for multi-wall carbon nanotubes and 10 mg/m3 for graphene. Consistent with the changes in lavage fluid, microgranulomas were observed at 2.5 mg/m3 multi-wall carbon nanotubes and 10 mg/m3 graphene. In order to evaluate volumetric loading of the lung as the key parameter driving the toxicity, deposited particle volume was calculated, taking into account different methods to determine the agglomerate density. However, the calculated volumetric load did not correlate to the toxicity, nor did the particle surface burden of the lung. Conclusions The inhalation toxicity of the investigated carbon-based materials is likely to be a complex interaction of several parameters. Until the properties which govern the toxicity are identified, testing by short-term inhalation is the best option to identify hazardous properties in

Inhaled 239PuO2 in rats with pulmonary emphysema

International Nuclear Information System (INIS)

Lundgren, D.L.; Mauderly, J.L.; Hahn, F.F.

1984-01-01

The modifying effects of a pre-existing lung disease (emphysema) on the deposition, distribution, retention, and effects of inhaled 239 PuO 2 in the rat are being investigated. Preliminary observations indicated that the deposition and retention patterns for 239 Pu particles inhaled by rats with emphysema and control rats were similar, but the distribution of inhaled 239 Pu immediately after exposure was different. Respiratory function measured through one year after exposure to 239 Pu was consistent with emphysema and was not altered by the 239 Pu lung burden. Long-term observations are continuing. 4 references, 2 tables

Puffing and inhalation behaviour in cigarette smoking: Implications for particle diameter and dose

Energy Technology Data Exchange (ETDEWEB)

Dickens, Colin; McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John, E-mail: colin_dickens@bat.co [British American Tobacco, Group R and D Centre, Southampton, SO15 8TL (United Kingdom)

2009-02-01

Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of diameter 150 - 250 nm CMD. Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, it was noted that particle deposition increased with increasing inhalation depth, and that smoke inhalation volumes were generally greater than normal tidal breathing volumes. A weak association was observed between particle diameter and puff flow, but no strong association between particle diameter and retention efficiency.

Puffing and inhalation behaviour in cigarette smoking: Implications for particle diameter and dose

International Nuclear Information System (INIS)

Dickens, Colin; McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John

2009-01-01

Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of diameter 150 - 250 nm CMD. Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, it was noted that particle deposition increased with increasing inhalation depth, and that smoke inhalation volumes were generally greater than normal tidal breathing volumes. A weak association was observed between particle diameter and puff flow, but no strong association between particle diameter and retention efficiency.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

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Diego J. Maselli

2017-05-01

Full Text Available The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM. These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

THE EFFECTS OF FINE LACTOSE AS A THIRD COMPONENT ON AEROSOLIZATION OF CEFOTAXIME SODIUM FROM DRY POWDER FORMULATIONS

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ABDOLHOSEIN ROUHOLAMINI NAJAFABADI

2006-06-01

Full Text Available Dry powder inhaler (DPI formulations usually contain micronized drug particles and lactose as a carrier. Fine lactose could be used as a ternary component to improve drug delivery from DPIs. The aim of this study was to investigate the deposition profile of a model drug, cefotaxime sodium (CS, using coarse and fine carriers after aerosolization at 60 l/min via a spinhaler® into a twin stage liquid impinger (TSI. Two micronization methods. jet milling and spray drying were used to micronize the active drug and carrier. The particle size of CS and lactose were characterized by laser diffraction, and the morphology of formulations was examined by scanning electron microscopy. X-ray diffraction of jet milled lactose showed crystalline nature, but spray dried lactose exhibited an amorphous state. The results showed the existence of fine lactose in formulations significantly (p0.05 difference was observed between the effect of jet milled and spray dried lactose. On the other hand selection of micronization technique to reduce particle size of CS, was very effective on deposition profile. The highest influence of fine lactose was obtained by formulation containing jet milled CS in ratio of drug/carrier 1/1 and 10% of fine lactose as third component.

Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system

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Hetal Thakkar

2011-01-01

Full Text Available Background : Raloxifene, a second-generation selective estrogen receptor modulator (SERM used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. Materials and Methods : In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM and in vitro intestinal permeability. Results : The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Conclusion : Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation.

Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system

Science.gov (United States)

Thakkar, Hetal; Nangesh, Jitesh; Parmar, Mayur; Patel, Divyakant

2011-01-01

Background: Raloxifene, a second-generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. Materials and Methods: In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS) formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM) and in vitro intestinal permeability. Results: The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Conclusion: Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation. PMID:21966167

Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke

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Hailian Wang

2016-01-01

Full Text Available Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms.

Formulation, Preparation, and Characterization of Polyurethane Foams

Science.gov (United States)

Pinto, Moises L.

2010-01-01

Preparation of laboratory-scale polyurethane foams is described with formulations that are easy to implement in experiments for undergraduate students. Particular attention is given to formulation aspects that are based on the main chemical reactions occurring in polyurethane production. This allows students to develop alternative formulations to…

Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

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Brittany K. Chavez

2016-01-01

Full Text Available Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 24 full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Thus, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.

The optimization of iloprost inhalation under moderate flow of oxygen therapy in severe pulmonary arterial hypertension.

Science.gov (United States)

Nakayama, Kazuhiko; Emoto, Noriaki; Tamada, Naoki; Okano, Mitsumasa; Shinkura, Yuto; Yanaka, Kenichi; Onishi, Hiroyuki; Hiraishi, Mana; Yamada, Shinichiro; Tanaka, Hidekazu; Shinke, Toshiro; Hirata, Ken-Ichi

2018-01-01

Inhaled iloprost efficiently improves pulmonary hemodynamics, exercise capacity, and quality of life in patients with pulmonary arterial hypertension (PAH). However, the process of inhalation is laborious for patients suffering from resting dyspnea. We describe a 75-year-old man with idiopathic PAH and a low gas transfer. Investigations excluded significant parenchymal lung disease and airflow obstruction (presuming FEV1/FVC ration > 70%). The patient struggled to complete iloprost inhalation due to severe dyspnea and hypoxemia. As such, we optimized the methods of oxygen supply from the nasal cannula to the trans-inhalator during the inhalation. We successfully shortened the inhalation duration that effectively reduced the laborious efforts required of patients. We also recorded pulmonary hemodynamics during inhalation of nebulized iloprost. This revealed significant hemodynamic improvement immediately following inhalation but hemodynamics returned to baseline within 2 hours. We hope that this optimization will enable patients with severe PAH to undergo iloprost inhalation.

Particle-size dependent effects in the Balb/c murine model of inhalational melioidosis

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Richard eThomas

2012-07-01

Full Text Available Deposition of Burkholderia pseudomallei within either the lungs or nasal passages of the Balb/c murine model resulted in different infection kinetics. The infection resulting from the inhalation of B. pseudomallei within a 12 um particle aerosol was prolonged compared to a 1 um particle aerosol with a mean time-to-death (MTD of 73.8 ± 11.3 h and 174.7 ± 14.9 h respectively. Inhalation of B. pseudomallei within 1 um or 12 um particle aerosols resulted in a median lethal dose (MLD of 4 and 12 cfu respectively. The 12 mm particle inhalational infection was characterised by involvement of the respiratory epithelium and inflammation of the neurological path leading from the olfactory epithelium to the olfactory bulb (100%, culminating in abscessation of the brain (33%. Initial involvement of the upper respiratory tract lymphoid tissues (nasal-associated lymphoid tissue and cervical lymph nodes was observed in both the 1 and 12 um particle inhalational infections (80-85%. Necrotising alveolitis and bronchiolitis were evident in both inhalational infections however lung pathology was greater after inhalation of the 1 mm particle aerosol with pronounced involvement of the mediastinal lymph node (50%. Terminal disease was characterised by bacteraemia in both inhalational infections with dissemination to the spleen, liver, kidneys and thymus. Treatment with co-trimoxazole was more effective than treatment with doxycycline irrespective of the size of the particles inhaled. Doxycycline was more effective against the 12 um particle inhalational infection as evidenced by increased time to death. However, both treatment regimes exhibited significant relapse when therapy was discontinued with massive enlargement and abscessation of the lungs, spleen and cervical lymph nodes observed.

Inhalation scan using sup(81m)Kr-gas

International Nuclear Information System (INIS)

Kobayashi, Hidetoshi; Sasaki, Tsuneo; Senda, Kohei; Ohara, Ken; Kaii, Osamu

1979-01-01

Inhalation scan using sup(81m) Kr-gas was performed in the various pulmonary diseases, in order to examine the ventilatory function of the lung after the measurement of ratio of expiratory ratio in the normal and diseased lung field. Inhalation scan is applied to the various pulmonary diseases such as lung cancer, radiation pulmonary fibrosis and chronic obstructive pulmonary disease. In cases of lung cancer, there is disturbance of respiratory function at the site of lesion when compared to the remainder of the normal lung fields. In cases of chronic obstructive pulmonary disease, the inhalation scan is performed at three states such as pre-, in- and post-attack of the disease. During the asthma attack the respiratory function is disturbed considerably when compared to the pre- and post-attack states. In each pulmonary disease, the ratio of expiratory ratio is measured from the histogram and pulmonary function is evaluated. (author)

Asthma Patients in US Overuse Quick-Relief Inhalers, Underuse Control Medications

Science.gov (United States)

... quick-relief inhalers, underuse control medications Share | Asthma patients in US overuse quick-relief inhalers, underuse control ... and uncontrolled asthma result in poor health outcomes. Patients with well-controlled asthma are at lower risk ...

Density-based global sensitivity analysis of sheet-flow travel time: Kinematic wave-based formulations

Science.gov (United States)

Hosseini, Seiyed Mossa; Ataie-Ashtiani, Behzad; Simmons, Craig T.

2018-04-01

Despite advancements in developing physics-based formulations to estimate the sheet-flow travel time (tSHF), the quantification of the relative impacts of influential parameters on tSHF has not previously been considered. In this study, a brief review of the physics-based formulations to estimate tSHF including kinematic wave (K-W) theory in combination with Manning's roughness (K-M) and with Darcy-Weisbach friction formula (K-D) over single and multiple planes is provided. Then, the relative significance of input parameters to the developed approaches is quantified by a density-based global sensitivity analysis (GSA). The performance of K-M considering zero-upstream and uniform flow depth (so-called K-M1 and K-M2), and K-D formulae to estimate the tSHF over single plane surface were assessed using several sets of experimental data collected from the previous studies. The compatibility of the developed models to estimate tSHF over multiple planes considering temporal rainfall distributions of Natural Resources Conservation Service, NRCS (I, Ia, II, and III) are scrutinized by several real-world examples. The results obtained demonstrated that the main controlling parameters of tSHF through K-D and K-M formulae are the length of surface plane (mean sensitivity index T̂i = 0.72) and flow resistance (mean T̂i = 0.52), respectively. Conversely, the flow temperature and initial abstraction ratio of rainfall have the lowest influence on tSHF (mean T̂i is 0.11 and 0.12, respectively). The significant role of the flow regime on the estimation of tSHF over a single and a cascade of planes are also demonstrated. Results reveal that the K-D formulation provides more precise tSHF over the single plane surface with an average percentage of error, APE equal to 9.23% (the APE for K-M1 and K-M2 formulae were 13.8%, and 36.33%, respectively). The superiority of Manning-jointed formulae in estimation of tSHF is due to the incorporation of effects from different flow regimes as

Formulation Changes Affect Material Properties and Cell Behavior in HA-Based Hydrogels

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Thomas Lawyer

2012-01-01

Full Text Available To develop and optimize new scaffold materials for tissue engineering applications, it is important to understand how changes to the scaffold affect the cells that will interact with that scaffold. In this study, we used a hyaluronic acid- (HA- based hydrogel as a synthetic extracellular matrix, containing modified HA (CMHA-S, modified gelatin (Gtn-S, and a crosslinker (PEGda. By varying the concentrations of these components, we were able to change the gelation time, enzymatic degradation, and compressive modulus of the hydrogel. These changes also affected fibroblast spreading within the hydrogels and differentially affected the proliferation and metabolic activity of fibroblasts and mesenchymal stem cells (MSCs. In particular, PEGda concentration had the greatest influence on gelation time, compressive modulus, and cell spreading. MSCs appeared to require a longer period of adjustment to the new microenvironment of the hydrogels than fibroblasts. Fibroblasts were able to proliferate in all formulations over the course of two weeks, but MSCs did not. Metabolic activity changed for each cell type during the two weeks depending on the formulation. These results highlight the importance of determining the effect of matrix composition changes on a particular cell type of interest in order to optimize the formulation for a given application.

Acute renal failure from inhalation of mycotoxins.

Science.gov (United States)

Di Paolo, N; Guarnieri, A; Loi, F; Sacchi, G; Mangiarotti, A M; Di Paolo, M

1993-01-01

Mysterious deaths of archeologists after opening Egyptian tombs have been suspected to be secondary to inhalation of mycotoxin, however, the hypothesis has never been verified. Recently, we observed a case of acute renal failure (ARF) undeniably due to inhalation of ochratoxin of Aspergillus ochraceus. After spending 8 h in a granary which had been closed for several months, a farmer and his wife suffered temporary respiratory distress; 24 h later, the woman developed nonoliguric ARF and biopsy revealed tubulonecrosis which healed in 24 days. Toxic substances were not found, but a strain of A. ochraceus producing ochratoxin was isolated from the wheat.

Influence of inhaler technique on asthma and COPD control: a multicenter experience

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Dudvarski Ilic A

2016-10-01

Full Text Available Aleksandra Dudvarski Ilic,1,2 Vladimir Zugic,1,2 Biljana Zvezdin,3,4 Ivan Kopitovic,3,4 Ivan Cekerevac,5,6 Vojislav Cupurdija,5,6 Nela Perhoc,7 Vesna Veljkovic,7 Aleksandra Barac8 1Faculty of Medicine, University of Belgrade, 2Clinic for Pulmonology, Clinical Centre of Serbia, Belgrade, 3Faculty of Medicine, University of Novi Sad, Novi Sad, 4Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, 5Faculty of Medicine, University of Kragujevac, 6Clinic for Pulmonology, Clinical Centre Kragujevac, Kragujevac, 7Clinic for Pulmonary Diseases Knez Selo, Clinical Centre Nis, Nis, 8Faculty of Stomatology, University Academy of Business Novi Sad, Novi Sad, Serbia Background: The successful management of asthma and chronic obstructive pulmonary disease (COPD mostly depends on adherence to inhalation drug therapy, the usage of which is commonly associated with many difficulties in real life. Improvement of patients’ adherence to inhalation technique could lead to a better outcome in the treatment of asthma and COPD.Objective: The aim of this study was to assess the utility of inhalation technique in clinical and functional control of asthma and COPD during a 3-month follow-up.Methods: A total of 312 patients with asthma or COPD who used dry powder Turbuhaler were enrolled in this observational study. During three visits (once a month, training in seven-step inhalation technique was given and it was practically demonstrated. Correctness of patients’ usage of inhaler was assessed in three visits by scoring each of the seven steps during administration of inhaler dose. Assessment of disease control was done at each visit and evaluated as: fully controlled, partially controlled, or uncontrolled. Patients’ subjective perception of the simplicity of inhalation technique, disease control, and quality of life were assessed by using specially designed questionnaires.Results: Significant improvement in inhalation technique was achieved after the

Study of physical and tribology properties of soybean oil-based grease formulated with polysoap

Science.gov (United States)

Soybean oil-based grease formulated with polysoaps, which was synthesized from polymeric epoxdized soybean oil, was investigated. Greases were prepared using a mixture of lithium soap and triethanolammonium polysoap. Grease properties investigated were: hardness, using cone penetration procedure (AS...

Modeling lung cancer risks in laboratory dogs exposed to inhaled plutonium

International Nuclear Information System (INIS)

Gilbert, E.S.; Park, J.F.; Buschbom, R.L.

1990-06-01

These analyses are based on data from a lifespan study of beagle dogs exposed to inhaled plutonium being conducted at Pacific Northwest Laboratory. An important goal of this study is to increase understanding of health risk resulting from this exposure, with particular attention to lung cancer risks. Data on humans exposed to plutonium are inadequate for achieving this goal

Inhalative cadmium effects in pregnant and fetal rats

Energy Technology Data Exchange (ETDEWEB)

Prigge, E.

1978-01-01

Pregnant and non-pregnant rats were continuously exposed for 21 days to an aerosol containing 0.2, 0.4, and 0.6 mg cadmium/m/sup 3/ air. Pregnant and non-pregnant rats exposed to clean air served as controls. The aerosol was generated by an ultrasonic nebulizer and was carried into inhalation chambers. The median aerodynamic diameters were on the order of 0.6 ..mu..m. After inhalation of cadmium aerosols, serum iron levels were not lowered significantly in adult rats. A polycythaemic response of non-pregnant rats was observed due to a direct stimulatory effect of cadmium on erythropoiesis. Polycythaemia was less marked in pregnancy, presumably due to iron loss to placenta and fetus. Disturbances of pulmonary gas exchange or decreased plasma volumes were excluded as causative mechanisms of polycythaemia. In pregnant rats there was a marked dose dependent decrease of the activity of the alkaline phosphatase after cadmium inhalation, while there was no effect in exposed non-pregnant rats. This decreased enzyme activity, together with slowed growth rates and hemolytic effect indicate a higher sensitivity to cadmium in pregnancy. Proteinuria was not found in neither pregnant nor non-pregnant rats. Therefore, it is concluded that in this respect cadmium intoxication by inhalation does not resemble human toxemia of pregnancy, as discussed in the literature.

New formulations of sunflower based bio-lubricants with high oleic acid content – VOSOLUB project

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Leao J. D.

2016-09-01

Full Text Available VOSOLUB project is a demonstration project supported by Executive Agency for Small and Medium-sized Enterprises (EASME that aims at testing under real operating conditions new formulations of sunflower-based biolubricants with high oleic acid content. These biolubricant formulations (including hydraulic fluids, greases, and neat oil metal-working fluids will be tested in three European demonstrating sites. Their technical performance will be evaluated and compared to corresponding mineral lubricants ones. In order to cover the demand for the sunflower base oil, a European SMEs network will be established to ensure the supply of the base at a competitive market price. Results presented concerns the base oil quality confirmed to be in accordance with the specification required, in particular on Free Fatty acid content, Phosphorus content, rancimat induction time and oleic acid content (ITERG. The oil characteristics specific for lubricant application analyzed by BfB Oil Research under normalized methods, match with lubricant specifications requirement such as viscosity, cold & hot properties, surface properties, anti-oxidant properties and thermal stability, anti-wear and EP properties, anti-corrosion properties Performance of the new biolubricant have been assessed by formulators and TEKNIKER First results on the use of new lubricant on real condition for rail Grease (produced by RS CLARE and tested with Sheffield Supertram, Hydraulic oil (produced by BRUGAROLAS and cutting oil (produced by MOTUL TECH and tested with innovative machining, turning are described.

Evaluation of personal inhalable aerosol samplers with different filters for use during anthrax responses.

Science.gov (United States)

Grinshpun, Sergey A; Weber, Angela M; Yermakov, Michael; Indugula, Reshmi; Elmashae, Yousef; Reponen, Tiina; Rose, Laura

2017-08-01

Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person's breathing zone. While a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. The goal of this study was to determine the best sampler-filter combination(s) for the collection and extraction of B. anthracis spores. The study was designed to (1) evaluate the performance of four filter types (one mixed cellulose ester, MCE (pore size = 3 µm), two polytetrafluoroethylene, PTFE (1 and 3 µm), and one polycarbonate, PC (3 µm)); and (2) evaluate the best performing filters in two commercially available inhalable aerosol samplers (IOM and Button). Bacillus thuringiensis kurstaki [Bt(k)], a simulant for B. anthracis, served as the aerosol challenge. The filters were assessed based on criteria such as ability to maintain low pressure drop over an extended sampling period, filter integrity under various environmental conditions, spore collection and extraction efficiencies, ease of loading and unloading the filters into the samplers, cost, and availability. Three of the four tested collection filters-except MCE-were found suitable for efficient collection and recovery of Bt(k) spores sampled from dry and humid as well as dusty and clean air environments for up to 8 hr. The PC (3 µm) filter was identified as the best performing filter in this study. The PTFE (3 µm) demonstrated a comparable performance, but it is more expensive. Slightly higher concentrations were measured with the IOM inhalable sampler which is the preferred sampler's performance criterion when detecting a highly pathogenic agent with no established "safe" inhalation exposure level. Additional studies are needed to address the effects of

Relationship between the use of inhaled steroids for chronic respiratory diseases and early outcomes in community-acquired pneumonia.

Directory of Open Access Journals (Sweden)

Jordi Almirall

Full Text Available BACKGROUND: The role of inhaled steroids in patients with chronic respiratory diseases is a matter of debate due to the potential effect on the development and prognosis of community-acquired pneumonia (CAP. We assessed whether treatment with inhaled steroids in patients with chronic bronchitis, COPD or asthma and CAP may affect early outcome of the acute pneumonic episode. METHODS: Over 1-year period, all population-based cases of CAP in patients with chronic bronchitis, COPD or asthma were registered. Use of inhaled steroids were registered and patients were followed up to 30 days after diagnosis to assess severity of CAP and clinical course (hospital admission, ICU admission and mortality. RESULTS: Of 473 patients who fulfilled the selection criteria, inhaled steroids were regularly used by 109 (23%. In the overall sample, inhaled steroids were associated with a higher risk of hospitalization (OR=1.96, p = 0.002 in the bivariate analysis, but this effect disappeared after adjusting by other severity-related factors (adjusted OR=1.08, p=0.787. This effect on hospitalization also disappeared when considering only patients with asthma (OR=1.38, p=0.542, with COPD alone (OR=4.68, p=0.194, but a protective effect was observed in CB patients (OR=0.15, p=0.027. Inhaled steroids showed no association with ICU admission, days to clinical recovery and mortality in the overall sample and in any disease subgroup. CONCLUSIONS: Treatment with inhaled steroids is not a prognostic factor in COPD and asthmatic patients with CAP, but could prevent hospitalization for CAP in patients with clinical criteria of chronic bronchitis.

Formulation of lubricating grease using Beeswax thickener