1,721,026 research outputs found
Resistant tuberculosis: The latest advancements of second-line antibiotic inhalation products
No full textDrug-resistant tuberculosis (TB) can be considered the man-made result of interrupted, erratic or inadequate TB therapy. As reported in WHO data, resistant Mycobacterium tuberculosis (Mtb) strains continue to constitute a public health crisis. Mtb is naturally able to survive host defence mechanisms and to resist most antibiotics currently available. Prolonged treatment regimens using the available first-line drugs give rise to poor patient compliance and a rapid evolution of strains resistant to rifampicin only or to both rifampicin and isonia-zid (multi drug-resistant, MDR-TB). The accumulation of mutations may give rise to extensively drug-resistant strains (XDR-TB), i.e. strains with resistance also to fluoroquinolones and to the injectable aminoglycoside, which represent the second-line drugs. Direct lung delivery of anti-tubercular drugs, as an adjunct to conventional routes, provides high concentrations within the lungs, which are the intended target site of drug delivery, representing an interesting strategy to prevent or reduce the development of drug-resistant strains. The purpose of this paper is to describe and critically analyse the most recent and advanced results in the formulation development of WHO second-line drug inhalation products, with particular focus on dry powder formulation. Although some of these formulations have been developed for other lung infectious diseases (Pseudomonas aeru-ginosa, nontuberculous mycobacteria), they could be valuable to treat MDR-TB and XDR-TB
Understanding the importance of capsules in dry powder inhalers
No full textPulmonary drug delivery is currently the focus of research and development because of its potential to produce maximum therapeutic benefit to patients by directing the drug straight to the lung disease site. Among all the available delivery options, one popular, proven and convenient inhaler device is the capsule-based dry powder inhaler (cDPI) for the treatment of an increasingly diverse range of diseases. cDPIs use a hard capsule that contains a powder formulation which consists of a mixture of a micronized drug and a carrier usually the lactose, known for its good lung tolerance. The capsule is either inserted into the device during manufacturer or by the patient prior to use. After perforating, opening or cut the capsule in the device, patients take a deep and rapid breath to inhale the powder, using air as the vector of drug displacement. The system is simple, relatively cheap and characterized by a lower carbon footprint than that of pressurized metered dose inhalers. This article reviews cDPI technology, focusing particularly on the importance of capsule characteristics and their function as a drug reservoir in cDPIs
Polysaccharides: New Frontiers for Nasal Administration of Medicines
No full textThe nasal cavity has become a focal point for drug delivery research. Beyond its use in treating local diseases, the nasal route is appealing due its ability to deliver systemically potent drugs with low oral bioavailability. Recent interest in nasal vaccination has driven significant pre-clinical and clinical advancements. Further R&D holds promise for expanding nasal medications, offering innovative healthcare solutions. This review explores strategies using polysaccharides to enhance nasal delivery of hydrophilic drugs, peptides, proteins, genes, and other active compounds that typically struggle to permeate the nasal epithelium. Polysaccharides are attractive excipients due to their potential to enhance nasal absorption, regulate drug release, and extend residence time in the nasal cavity through bioadhesive properties. Studies on their mechanisms affecting drug absorption, potential toxicities, and applications will also be reviewed considering the particularities of nasal epithelium anatomy and physiology. Most products with these excipients are in pre-clinical and clinical evaluation, but PecFent, a pectin-based formulation, is approved for nasal administration of opioids for breakthrough cancer pain, offering faster pain relief and a better benefit–risk ratio due to pectin. Other polysaccharides like chitosan, cyclodextrins, hyaluronic acid, and alginate have shown potential in enhancing nasal drug absorption. This approach also holds promise for enhancing drug transport from the nasal cavity to the CNS (nose-to-brain), potentially advancing treatments for neurodegenerative diseases
Long-acting inhaled medicines: Present and future
No full textInhaled medicines continue to be an essential part of treatment for respiratory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. In addition, inhalation technology, which is an active area of research and innovation to deliver medications via the lung to the bloodstream, offers potential advantages such as rapid onset of action, enhanced bioavailability, and reduced side effects for local treatments. Certain inhaled macromolecules and particles can also end up in different organs via lymphatic transport from the respiratory epithelium. While the majority of research on inhaled medicines is focused on the delivery technology, particle engineering, combination therapies, innovations in inhaler devices, and digital health technologies, researchers are also exploring new pharmaceutical technologies and strategies to prolong the duration of action of inhaled drugs. This is because, in contrast to most inhaled medicines that exert a rapid onset and short duration of action, long-acting inhaled medicines (LAIM) improve not only the patient compliance by reducing the dosing frequency, but also the effectiveness and convenience of inhaled therapies to better manage patients' conditions. This paper reviews the advances in LAIM, the pharmaceutical technologies and strategies for developing LAIM, and emerging new inhaled modalities that possess a long-acting nature and potential in the treatment and prevention of various diseases. The challenges in the development of the future LAIM are also discussed where active research and innovations are taking place
Mannitol polymorphs as carrier in dpis formulations: Isolation characterization and performance
Full text linkThe search for best performing carriers for dry powder inhalers is getting a great deal of interest to overcome the limitations posed by lactose. The aerosolization of adhesive mixtures between a carrier and a micronized drug is strongly influenced by the carrier solid-state properties. This work aimed at crystallizing kinetically stable D-mannitol polymorphs and at investigating their aerosolization performance when used in adhesive mixtures with two model drugs (salbutamol sulphate, SS, and budesonide, BUD) using a median and median/high resistance inhaler. A further goal was to assess in vitro the cytocompatibility of the produced polymer-doped mannitol polymorphs toward two lung epithelial cell lines. Kinetically stable (up to 12 months under accelerate conditions) α, and δ mannitol forms were crystallized in the presence of 2% w/w PVA and 1% w/w PVP respectively. These solid phases were compared with the β form and lactose as references. The solid-state properties of crystallized mannitol significantly affected aerosolization behavior, with the δ form affording the worst fine particle fraction with both the hydrophilic (9.3 and 6.5%) and the lipophilic (19.6 and 32%) model drugs, while α and β forms behaved in the same manner (11–13% for SS; 53–58% for BUD) and better than lactose (8 and 13% for SS; 26 and 39% for BUD). Recrystallized mannitol, but also PVA and PVP, proved to be safe excipients toward lung cell lines. We concluded that, also for mannitol, the physicochemical properties stemming from different crystal structures represent a tool for modulating carrier-drug interaction and, in turn, aerosolization performance
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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