1,720,971 research outputs found
POWDER COMPOSITION BASED ON MICROPARTICLES EMBEDDING NANOPARTICLES FOR THE DELIVERY OF THERAPEUTIC/DIAGNOSTIC COMPOUNDS
No full textThe Impact of Possible Misuses Conditions on in Vitro Performance of NEXThaler in Comparison with Ellipta Inhaler
No full text: The correct use of dry powder inhalers by the patients is essential to ensure effective treatment and management of the disease. The purpose of the work was to assess the consequence of inhaler misuse in terms of emitted dose and aerodynamic parameters. One reservoir multidose (Foster-NEXThaler®) and one pre-dosed (Relvar-Ellipta®) devices, both sharing the "open, inhale and close" procedure, were the subject of the study. NEXThaler activated at different degrees of slope showed a consistent dose delivery for both the drugs included in the formulation (beclomethasone dipropionate/formoterol fumarate). Contrary, Ellipta showed a decrease of the emitted dose for both fluticasone furoate and vilanterol trifenatate when the device was operated with inclination (-14% at 45° and -22% at 90°). Similarly, the delivered dose of NEXThaler was unaffected by an accidental fall, while Ellipta released FluF and VT doses 50% lower than the control values. The presence of the dose protector in NEXThaler offers the advantage of retaining the powder if the inhaler is subjected to incorrect manipulations. Both products proved to be reliable in double activation. Finally, simulation exhalation conditions had an impact on the aerodynamic profile of the two products
Dry powder inhaler of colistimethate sodium for lung infections in cystic fibrosis: optimization of powder construction
No full textColistimethate sodium (CMS) for treatment of lung infections in cystic fibrosis patient was transformed into a dry powder for inhalation by spray drying. Design of Experiment was applied for understanding the role of the spray-drying process parameters on the critical quality attributes of the CMS spray-dried (SD) powders and agglomerates thereof. Eleven experimental SD microparticle powders were constructed under different process conditions according to a central composite design. The SD microparticles were then agglomerated in soft pellets. Eleven physico-chemical characteristics of SD CMS microparticle powders or agglomerates thereof were selected as critical quality attributes. The yield of SD process was higher than 75%. The emitted fraction of agglomerates from RS01 inhaler was 75–84%, and the fine particle fraction (particles <5 μm) was between 58% and 62%. The quality attributes of CMS SD powders and respective agglomerates that were significantly influenced by spray-drying process parameters were residual solvent and drug content of the SD microparticles as well as bulk density and respirable dose of the agglomerates. These attributes were also affected by the combination of the process variables. The air aspiration rate was found as the most positively influential on drug and solvent content and respirable dose. The residual solvent content significantly influenced the powder bulk properties and aerodynamic behavior of the agglomerates, i.e. quality attributes that govern drug metering in the device and the particles lungs deposition. Agglomerates of CMS SD microparticles, in combination with RS01 DPI, showed satisfactory results in terms of dose emitted and fine particle fraction
Dry powder inhaler of colistimethate sodium for lung infections in cystic fibrosis: optimization of powder construction
No full textColistimethate sodium (CMS) for treatment of lung infections in cystic fibrosis patient was transformed into a dry powder for inhalation by spray drying. Design of Experiment was applied for understanding the role of the spray-drying process parameters on the critical quality attributes of the CMS spray-dried (SD) powders and agglomerates thereof. Eleven experimental SD microparticle powders were constructed under different process conditions according to a central composite design. The SD microparticles were then agglomerated in soft pellets. Eleven physico-chemical characteristics of SD CMS microparticle powders or agglomerates thereof were selected as critical quality attributes. The yield of SD process was higher than 75%. The emitted fraction of agglomerates from RS01 inhaler was 75-84%, and the fine particle fraction (particles <5 mu m) was between 58% and 62%. The quality attributes of CMS SD powders and respective agglomerates that were significantly influenced by spray-drying process parameters were residual solvent and drug content of the SD microparticles as well as bulk density and respirable dose of the agglomerates. These attributes were also affected by the combination of the process variables. The air aspiration rate was found as the most positively influential on drug and solvent content and respirable dose. The residual solvent content significantly influenced the powder bulk properties and aerodynamic behavior of the agglomerates, i.e. quality attributes that govern drug metering in the device and the particles lungs deposition. Agglomerates of CMS SD microparticles, in combination with RS01 DPI, showed satisfactory results in terms of dose emitted and fine particle fraction
Consequences of not-shaking and shake-fire delays on the emitted dose of some commercial solution and suspension pressurized metered dose inhalers
Full text linkPressurized metered-dose inhalers (pMDIs) include hydrofluoroalkane (HFA) propellant to generate a drug aerosol upon actuation and drugs can be formulated as solution or suspension. Suspended particles can cream or sediment depending on density differences between drug and propellant and shaking the pMDI is an essential step to ensure a uniform drug dose release
Orphan Designation and Cisplatin/Hyaluronan Complex in an Intracavitary Film for Malignant Mesothelioma
Full text linkPleural mesothelioma is a lung diffuse tumor, whose complete resection is unlikely. Consequently,
metastases reappear where the primary tumor was removed. This paper illustrates the
orphan medicine designation procedure of an intracavitary cisplatin film and related pharmaceutical
development aspects requested by the European Medicines Agency (EMA) in its Scientific
Advice. Since cisplatin pharmacokinetics from the implanted film in sheep resulted substantially
modified compared to intravenous administration, the formation of a cisplatin/hyaluronan complex
had been hypothesized. Here, the interaction between sodium hyaluronate (NaHA) and cisplatin
(CisPt) was demonstrated. Size exclusion chromatography qualitatively evidenced the complex
in the film-forming mixture, only showing the NaHA peak. Atomic absorption spectroscopy of
the corresponding fraction revealed platinum, confirming the interaction. Reverse phase HPLC
quantified about 5% free cisplatin in the film-forming mixture, indirectly meaning that 95% was
complexed. Finally, a study of CisPt release from the film assessed how CisPt/NaHA complex
affected drug availability. In water, a medium without chloride ions, there was no release and the
film remained intact for 48 h and longer, whereas the placebo film dissolved in 15 min. In 0.9% NaCl
medium, the film became more soluble, dissolving within 3–4 h. However, cisplatin release was
still controlled by the existing complex in solution until chloride ions displaced it. While the film
modified its dissolution with aging, CisPt release remained unaffected (90% released in 48 h)
Nasal inhalation of antiviral microparticulate powders to target early infection of upper airways
No full textDuring the COVID-19 pandemic, several compounds among which chloroquine diphosphate (CqP), have been repurposed as anti-SARS-CoV-2 drugs. Critically, studies were most often performed by systemic drug administration, whereas the early viral infection of human body appeared in the upper respiratory tract. This research addressed the delivery strategy for depositing a powder aerosol of CqP onto the upper airways by a nasal inhalation act. By formulating the drug as nasal microparticulate aerodynamic powder, the loco-regional application of particle aerosol concentrates the drug primarily on the upper airway epithelia where the virus replicates. Nasal microparticulate powders of CqP, with and without excipients, were engineered by spray drying, obtaining particle size, density and morphology suitable for aerosolization and deposition onto the upper respiratory tract. The powders were loaded into a pre-metered device for oral inhalation of dry powders that was innovatively actuated by a nasal sharp sniff. The generated nasal airflow, measured in healthy volunteers, enabled powder dose emission from the inhaler. Chloroquine diphosphate microparticles, deposited on rabbit nasal mucosa ex vivo, led in less than 45 min to CqP concentrations within the epithelial cells between 30-70 mM. The in vitro CqP concentrations inhibiting SARS-CoV-2 replication, were in the mu M range. The virus inhibition studied in Vero E6 cells was further enhanced when the cells were pre-treated with the drug powder before infection. In conclusion, the simple nasal sniff of an antiviral aerodynamic powder could be active against airborne viral early infection, limiting the exposition of the whole body to undesired drug effects
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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