1,721,002 research outputs found
Solid lipid microparticles as an approach to drug delivery
No full textIntroduction : Solid lipid particles have been introduced since the early 1990s as an alternative drug carrier system to emulsions, liposomes and polymeric microparticles. While lipid nanoparticles have been examined/the object of a substantial number of reviews, fewer are available on lipid microparticles despite their distinct advantages, including biocompatibility, ease of production and characterization, extended release properties and high loading.
Areas covered : This review presents an overview of the advantages and drawbacks of lipid microparticles (LMs), i.e. lipid-based particles with dimensions in the micrometer range. Specific focus is on the role of the main excipients used for LMs formulations, lipids and surfactants, and their effect on LM properties. Furthermore, an update on preparation techniques and characterization methods are also presented, with particular emphasis on more recent technologies. The interaction of LMs with biological systems, and in particular with cells will be also reviewed. Moreover, the various LM administration routes will be examined, with special attention to most recent applications (i.e., pulmonary and nasal delivery).
Expert opinion: LMs represents an attractive and versatile carrier system, however their pharmaceutical applicability has been rather limited. Investigation on the use of LMs for less established administration routes, such as pulmonary delivery, may provide further interest on the development of LM-based systems both in the industry and in the clinics
Evolved gas analysis during thermal degradation of salbutamol sulphate
Full text linkCrystalline salbutamol sulphate (SS) is a common β2-agonist used in dry powder inhalers for the treatment of asthma. The solid-state characteristics of SS are import since they govern the stability, and thus efficacy of the drug when incorporated in inhalation medicine. Previous studies have investigated the thermal properties of SS and the complex array of thermal events have been attributed a mixture of melting and/or degradation mechanisms. In order to ascertain the exact thermal transformation processes that SS undergoes, and we utilised a combination of differential scanning calorimetry coupled with quadrupole mass spectrometry and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy over the temperature range 25-500 °C. Based on the coupled thermal analysis data, we proposed that SS undergoes a multi-step degradation mechanism in which the molecule dehydrates loosing water initially, followed by the break up of the secondary amine group and lastly formation of sulphur dioxide. When used in conjunction, the analytical techniques offered significant advantages over the use of thermal analysis alone, offering a better understanding of the transformations occurring to SS following heating
Antibiotic transport across bronchial epithelial cells: Effects of molecular weight, LogP and apparent permeability
No full textPurpose The first step in developing a new inhalable formulation for the treatment of respiratory diseases is to understand the mechanisms involved in the absorption of drugs after lung deposition. This information could be important for the treatment of bacterial infection in the lung, where low permeability would probably be beneficial, or a systemic infection, where high permeability would be desirable. The goal of this study was to evaluate the transport of several antibiotics (ciprofloxacin, azithromycin, moxifloxacin, rifampicin, doxycycline and tobramycin) across human bronchial airway epithelium and to study the influence of molecular weight and LogP on the apparent permeability. Methods The experiments were conducted using Calu-3 cells seeded in the apical compartment of 24-well Transwell® inserts. The antibiotics transport was measured in both apical to basolateral (A-B) and basolateral to apical (B-A) directions and the apparent permeability of each antibiotic was calculated. Results The A-B transport of ciprofloxacin and rifampicin was independent of the initial concentration in the donor compartment, suggesting the involvement of active transporters in their absorption. Moxifloxacin, doxycycline, azithromycin and tobramycin presented a low absorptive permeation in the A-B direction, indicating that these substances could be substrate for efflux pumps. Generally, all antibiotics studied showed low permeabilities in the B-A direction. Conclusions These findings suggest that the inhalation route would be favorable for delivering these specific antibiotics for the treatment of respiratory infection, compared with present oral or intravenous administration
The formulation of a novel macrolide solution pressurised metered dose inhaler: the use of Clarithromycin as an anti-inflammatory for bronchiectasis therapy
No full textSeveral studies have corroborated that clarithromycin, a macrolide antibiotic, has antinflammatory effects in respiratory diseases. The formulation and characterisation of a clarithromycin pressurised metered dose inhaler (pMDI) solutions was investigated. The novel solution pMDI had suitable aerosol properties for lung delivery. It demonstrated to be non toxic at the administered doses and had in vitro inhibitory effects on mucus secretion of Calu-3 cells
The development of a single-use, capsule-free multi-breath tobramycin dry powder inhaler for the treatment of cystic fibrosis
No full textThe aerosol performance and delivery characteristics of tobramycin for the treatment of respiratory infection were evaluated using the OrbitalTM, a multi-breath, high dose, dry powder inhaler (DPI). Micronised tobramycin was prepared and tested in the Orbital and in the commercially available TOBI Podhaler (Novartis AG). Furthermore, the TOBI Podhaler formulation containing tobramycin as Pulmospheres was tested in both the commercial Podhaler device (T-326) and Orbital for comparison. By varying the puck geometry of the Orbital, it was possible to deliver equivalent doses of micronised tobramycin (114.09 ± 5.86 mg) to that of the Podhaler Pulmosphere product (116.01 ± 2.59 mg) over 4 sequential simulated breaths (60 L min−1 for 4 s) without the need for multiple capsules. In general, the aerosol performance of the micronised tobramycin from the Orbital was higher than the T-326 Podhaler device, with fine particle fraction (FPF) of 44.99% ± 1.09% and 37.03% ± 0.86%, respectively. When testing the Pulmosphere powder in the two devices, the T-326 had marginally better performance with a FPF of 68.77% ± 2.10% compared to 61.30% ± 3.45%. This is to be expected since the TOBI Podhaler and Pulmosphere are an optimised powder and device combination. The Orbital was shown to be capable of delivering high efficiency, high dose antibiotic therapy for inhalation without the need for the use of multiple capsules as used in current devices. This approach may pave the way for a number of antibiotic therapies and medicaments where high dose respiratory deposition is required
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
Co-spray dried resveratrol and budesonide inhalation formulation for reducing inflammation and oxidative stress in rat alveolar macrophages
No full textOxidative stress is instrumental in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Novel therapeutic strategies that target macrophages, based on the use of antioxidant compounds, could be explored to improve corticosteroids responses in COPD patients. In this study, inhalable microparticles containing budesonide (BD) and resveratrol (RES) were prepared and characterized. This approach was undertaken to develop a multi-drug inhalable formulation with anti-oxidant and anti-inflammatory activities for treatment of chronic lung diseases. The inhalable microparticles containing different ratio of BD and RES were prepared by spray drying. The physico-chemical properties of the formulations were characterized in terms of surface morphology, particle size, physical and thermal stability. Additionally, in vitro aerosol performances of these formulations were evaluated with the multi-stage liquid impinger (MSLI) at 60 and 90 l/min, respectively. The cytotoxicity effect of the formulations was evaluated using rat alveolar macrophages. The biological responses of alveolar macrophages in terms of cytokine expressions, nitric oxide (NO) production and free radical scavenging activities were also tested. The co-spray dried (Co-SD) microparticles of all formulations exhibited morphologies appropriate for inhalation administration. Analysis of the deposition profiles showed an increase in aerosol performance proportional to BD concentration. Cell viability assay demonstrated that alveolar macrophages could tolerate a wide range of RES and BD concentrations. In addition, RES and BD were able to decrease the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS) induced alveolar macrophages.
This study has successfully established the manufacture of Co-SD formulations of RES and BD with morphology and aerosol properties suitable for inhalation drug delivery, negligible in vitro toxicity and enhanced efficacy to control inflammation and oxidative stress in LPS-induced alveolar macrophages
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