Aerosol Drug Delivery Research Articles

A Prodrug Approach toward the Development of Water Soluble Fluoroquinolones and Structure−Activity Relationships of Quinoline-3-carboxylic Acids

A fluoroquinolone prodrug, PA2808, was prepared and shown to convert to the highly active parent drug PA2789. In vitro and in vivo activation of PA2808 by alkaline phosphatase was demonstrated using disk diffusion and rat lung infection models. The water solubility of PA2808 showed a marked increase compared to PA2789 over a pH range suitable for aerosol drug delivery. A total of 48 analogues based on PA2789 were prepared and screened against a panel of Gram-positive and Gram-negative pathogens. Incorporating a cyclopropane-fused pyrrolidine (amine) at C-7 resulted in some of the most active analogues.

PARTICLE DEPOSITION IN AIRWAY BIFURCATIONS IN DIFFERENT BREATHING CONDITIONS

During inhaling, the particles transported in the gas mixture may deposit onto the walls of the respiratory tract. Deposition rates depend on particle size, breathing pattern and air duct geometry (Bejan et al. 2004). People suffering from respiratory diseases, such as allergy and asthma and from cardiovascular problems have been identified to be particularly sensitive to inhalation of particulate matter. On the other hand, inhalation route for drug aerosol delivery is a very suitable technique for the treatment of respiratory disorders and other health problems. Toxicology and therapeutic health effects of aerosol particles is strong dependent upon deposition patterns in the respiratory tree. Multi-dimensional simulations of particle transport and deposition in the respiratory tract have been performed by several authors (see, for example, Bejan et al. 2004). Despite its importance, very few studies deal with the experimental determination of aerosol transport and deposition in bifurcating airways. This is partially due to the difficulty in performing the experiments. In this paper, particle deposition in a rigid double bifurcation airway is studied experimentally. The effect of particle size and breathing conditions in the deposition are analyzed. Besides, the effect of airway obstruction (local reduction of airway diameter) that can be originated by some respiratory disorders is also studied. The experiments were performed in conditions of humidity near saturation in order to account for the conditions occurring in the respiratory tree (Bejan et al. 2004).

A CFD study of the throat during aerosol drug delivery using heliox and air

Deposition of a series of monodisperse aerosol injections in 70/30 helium/oxygen (Heliox) and air for the larynx and trachea was numerically analyzed with Computational Fluid Dynamics (CFD) software. The CFD mesh was prepared from a cadaver-based throat (female, aged 84). Monosize droplets ranging between 0.25 and 10 μm in droplet radius were used for both Heliox and air simulations. The coupled simulation was performed with the KIVA-3V software for a flow rate of 18 l/ min , an approximate adult breathing condition. Flow measurements were validated against previous experimental simulations of this cadaver model. It was found that Heliox and air had highly similar flow structures in the simulated region. Flow measurements such as turbulent kinetic energy and velocity magnitude typically differed by less than 5%. Particle deposition was shown to be affected by these small differences in the carrier gas. The use of Heliox led to less particle deposition for all droplet sizes indicating that Heliox will lead to a reduction of in vivo extrathoracic deposition due to the intrinsic properties of the gas phase. This numerical simulation suggests that a continuous Heliox phase provides a stronger steering force to the discrete phase.

Aerosolized Antibiotics in Cystic Fibrosis

Inhaled antibiotics offer an attractive alternative to systemic administration in cystic fibrosis (CF) for several reasons. Antibiotics can be administered directly to the site of infection with little systemic absorption, thereby minimizing toxicity. Aerosolization will permit chronic administration of antipseudomonal antibiotics while avoiding the risks and inconvenience of intravenous access. Modern aerosolized drug delivery systems enable endobronchial delivery of very high antibiotic concentrations, resulting in clinical improvement even in patients with bacterial organisms that traditionally would have been considered resistant. This article summarizes basic concepts of aerosol drug administration and reviews available data on the administration of a variety of drug classes for both suppressive therapy and acute exacerbations of cystic fibrosis, including toxicity and safety data. The aminoglycosides have been by far the most extensively studied class of antibiotics, culminating in U.S. Food and Drug Administration (FDA) approval of a specifically formulated tobramycin solution for inhalation. The available data on the development of antibiotic resistance and emergence of other organisms with long-term use of this agent are reviewed. Finally, a brief guideline for initiating and monitoring patients on antibiotic aerosols is provided for the clinician caring for CF patients.

Growth inhibition of established B16-F10 lung metastases by sequential aerosol delivery of p53 gene and 9-nitrocamptothecin.

Growth inhibition of established tumor metastases in the lungs poses a difficult challenge for most clinical settings in spite of extensive multi-modality approaches. Aerosol delivery of drugs and genes holds promise for the treatment of disseminated lung metastases, since aerosol delivery can target the lungs specifically and uniformly. We previously demonstrated that aerosol delivery of dilauroylphosphatidylcholine liposome formulation of 9-nitrocamptothecin (9NC-DLPC) inhibits B16-F10 melanoma lung metastases. Aerosol delivery of polyethleneimine-p53 DNA (PEI-p53) complexes results in a similar anti-tumor effect in the B16-F10 model. In both these previous studies, the protocols were designed to inhibit development of lung metastases. In this study we demonstrate, using the B16-F10 melanoma lung metastasis model, that sequential aerosol delivery of PEI-p53 and 9NC-DLPC acts additively to inhibit growth of established B16-F10 tumor metastases in the lungs. Mice injected with B16-F10 cells and treated with a combination of 9NC-DLPC (twice weekly) and PEI-p53 (once weekly) aerosol complexes starting on day 11 after tumor inoculation, exhibited a highly significant (P < 0.01) reduction in the number of visible tumor foci as compared with untreated mice or mice treated with either single agent alone, or with a combination of 9NC and a control plasmid. There was a highly significant reduction in the tumor burden, as well as the lung weights for the 9NC and p53 combination group (P < 0.001 as compared with other groups). Moreover, the doses of p53 gene and 9NC in the combination group were reduced at least two-fold as compared with our previous single agent studies, but still achieved significant tumor inhibition. Furthermore, the sequential aerosol delivery of p53 and 9NC lead to a 30-40% increase in the mean survival time of these mice, as compared with animals in different control groups. The data suggest that the combination of 9NC and p53 gene delivered by aerosol is an attractive strategy for growth inhibition of established tumor metastases in the lungs.

Pharmaceutical considerations in aerosol drug delivery.

Aerosolized drug delivery has been used for over 50 years, but its quality and scope continue to increase. Three factors affect this form of drug delivery: the nebulizer, the compressor, and the actual drug preparation. As technology and knowledge improve, this delivery system also improves. Patients with cystic fibrosis, in particular, can benefit significantly from this form of therapy.

Transient airflow structures and particle transport in a sequentially branching lung airway model

Considering oscillatory laminar incompressible three-dimensional flow in triple planar and nonplanar bifurcations representing generations three to six of the human respiratory system, air flow fields and micron-particle transport have been simulated under normal breathing and high-frequency ventilation (HFV) conditions. A finite-volume code (CFX4.3 from AEA Technology, Pittsburgh, PA) and its user-enhanced FORTRAN programs were validated with experimental velocity data points for a single bifurcation. The airflow structures and micron-particle motion in the triple bifurcations were analyzed for a representative normal breathing cycle as well as HFV condition. While both the peak inspiratory and expiratory velocity profiles for the low Womersley case (α=0.93) agree well with those of instantaneously equivalent steady-state cases, some differences can be observed between flow acceleration and deceleration at off-peak periods or near flow reversal, especially during inspiratory flow. Similarly, the basic features of instantaneous particle motion closely resemble the steady-state case at equivalent inlet Reynolds numbers. The preferential concentration of particles caused by the coherent vortical structures was found in both inhalation and exhalation; however, it is more complicated during expiration. The effects of Womersley number and non-planar geometries as well as the variations in secondary flow intensity plus pressure drops across various bifurcations under normal breathing and HFV conditions were analyzed as well. This work may elucidate basic physical insight of aerosol transport relevant in dosimetry-and-health-effect studies as well as for drug aerosol delivery analyses.

Jet nebulization of PEI/DNA polyplexes: physical stability and in vitro gene delivery efficiency.

Aerosol drug delivery currently represents the most acceptable and convenient delivery system for repeated drug application to the lungs. Although polyethyleneimine (PEI) has recently been demonstrated to mediate gene transfer successfully to mouse lungs via aerosol delivery, the effect of the jet nebulization process on the properties of PEI/DNA polyplexes has not yet been examined. PEI/DNA polyplexes were generated in several commonly used solvents, such as distilled water, HEPES buffered saline (HBS), and 5% glucose. The complex parameters, such as particle size, zeta potential, DNA integrity, and transfection efficiency, were examined before and after jet nebulization. The complex parameters and the transfection efficiency were influenced by the solvent that was used for complex formulation and by the nebulization process itself. When polyplexes were formulated in HBS, the particle size, zeta potential, and DNA concentration were affected by the nebulization process and the transfection efficiency decreased dramatically. Polyplexes formulated in 5% glucose were less susceptible to the nebulization process, as indicated by only minor changes of the zeta potential and particle size when compared with HBS. The resulting transfecion efficiency was very low both before and after nebulization. Polyplexes formulated in distilled water had the most resistant behavior with the nebulization process. Zeta potential, particle size, and DNA integrity were influenced least of all by nebulization. As a result, the transfection efficiency of PEI/DNA complexes remained constant throughout the nebulization process only when formulated in distilled water. These data suggest that distilled water represents the most appropriate solvent for polyplex formulation when delivered by jet nebulization.

Microbiological and Immunologic Considerations With Aerosolized Drug Delivery

The development of drug resistance is a major theoretical concern with the long-term delivery of aerosolized antibiotics via inhalation. A randomized, placebo-controlled, double-blind study, which compared inhaled tobramycin plus standard cystic fibrosis (CF) care to placebo plus standard CF care, examined the following microbiological parameters: percentage of patients with at least one Pseudomonas aeruginosa (PA) strain with a minimal inhibitory concentration (MIC) > 16 microg/mL (ie, the breakpoint for tobramycin resistance delivered by the parenteral route); changes in the levels of the lowest concentration required to inhibit the growth of 50% of strains tested (MIC(50)) and 90% of strains tested (MIC(90)); the percentage of patients with an increase, decrease, or change in the MIC of the most resistant and most prevalent PA strains; and the percentage of patients in whom the PA strain with the highest MIC also was the most prevalent. During the first 6 months, which included three on-drug and off-drug cycles of 4 weeks' duration each, the percentage of tobramycin-treated patients with at least one PA isolate and with an MIC > 16 microg/mL was 13% at baseline, 26% at 20 weeks, and 23% at 24 weeks vs 10%, 17%, and 8%, respectively, for placebo-treated patients. No significant change was observed in MIC(50) at 20 and 24 weeks. The increase in MIC(90) was not statistically significant. At 24 weeks, there was no increase in the percentage of patients in either group in whom the PA strain with the highest MIC became most the prevalent strain. After the third on-drug cycle, 33% of the tobramycin group showed an increase in the MIC of the strain with the highest MIC. This decreased to 26% after 1 month off drug therapy. A preliminary analysis of the 12-month and 18-month data showed a decrease in the proportion of resistant PA isolates after each off-drug cycle. This return to susceptibility following an off-drug cycle was not observed at 24 months. The mechanism of resistance in this setting is believed to be increased impermeability to drug. At all time points, pulmonary function improved even in patients with MICs of > or = 128 microg/mL. At 6 months, no increase was seen in the rates of superinfection with tobramycin-resistant, Gram-negative pathogens. Increases in Stenotrophomonas maltophilia were detected in patients after 18 and 24 months of tobramycin therapy and were similar to those rates in patients receiving placebo. These rates may be independent of inhalation therapy.

Formulation of Aerosolized Therapeutics

Pseudomonas aeruginosa (PA), which colonizes the airways of approximately 90% of patients with cystic fibrosis (CF) at some point during their lives, is an important contributor to the vicious cycle of infection and inflammation leading to bronchiectasis and eventual respiratory failure. Oral antibiotic therapy is often ineffective in treating PA infections. Instead, in-hospital IV aminoglycoside therapy administered in combination with other IV antibiotics, such as beta-lactams or quinolones, is the mainstay of treatment. The specific chemical and physical properties of CF sputum require high serum antibiotic levels for effective antimicrobial treatment; however, IV aminoglycoside therapy is associated with an increased risk of ototoxicity and nephrotoxicity. In an attempt to avoid systemic toxicity and effectively treat PA infections, clinicians have combined IV antibiotics with sterile solutions of saline or water to aerosolize the mixture for inhalation. Experience with such "home brews" has clearly demonstrated that IV preparations are neither intended nor medically indicated for inhalation. Patients may experience coughing, mucosal irritation, or bronchospasm in response to the preservatives, stabilizing agents, and other additives commonly found in IV preparations. While the rationale for aerosolized drug delivery remains compelling, concerns about uniform dose delivery, ineffective nebulization, and therapeutic adherence arise. Since the 1940s, when these efforts began, ongoing research and clinical trials have identified several additional factors affecting inhaled drug delivery and deposition in the airways. This article chronicles some of the challenges faced by researchers and elucidates factors critical to the reformulation of a safe and effective antibiotic solution for aerosolized delivery.

Oral endotracheal intubation of rats for intratracheal instillation and aerosol drug delivery.

As reported in the literature, oral endotracheal intubation of rats is considered to be very difficult. Specialised equipment and complicated techniques have been described to perform this procedure. In our experiment we adopted a simple method, which allowed-without any complicated equipment-the insertion of a relatively wide tube into the trachea of rats, allowing drug administration.

Invited commentary

Delivery of therapeutic agents via intratracheal administration is an attractive strategy for the treatment and prevention of aerodigestive tract cancers, as well as the prevention of ischemia-reperfusion injury and acute rejection following lung transplantation. Relative to viral delivery systems, naked plasmid vectors are markedly less efficient with regard to gene transfer to respiratory epithelia. However, plasmid vectors are easier and less costly to produce in large quantity, and are significantly less immunogenic than viral vectors; hence naked plasmid vectors may be utilized for repeated administration. Although presently not applicable for gene therapy of pulmonary neoplasms, naked plasma vectors expressing cytokines which function by paracrine mechanisms may be effective in attenuating the inflammatory processes associated with ischemia-reperfusion, or allograft rejection within the lung. The authors of the present study have extensive experience in clinical pulmonary transplantation. These individuals have previously demonstrated direct gene transfer of heat shock protein-70 or nitric oxide synthetase can reduce ischemia-reperfusion, and have reported that transfection of naked plasmid expressing TGF-β1 reduces acute rejection in animal lung transplant models. In the present study, these investigators examined the transfection efficiency of two plasmid vectors administered simultaneously prior to allograft harvest, and ascertained the effects of cold preservation on reporter gene expression following transplantation. The data indicated that naked plasmid vectors expressing multiple gene products could be delivered via intratracheal administration. Not surprisingly, exposure duration enhanced transfection efficiency. Cold ischemia diminished the transfection efficiency of naked plasmid vectors; however, if pulmonary harvest was delayed to enable uptake and transport of plasmid DNA to the nucleus, cold ischemia did not appear to diminish reporter gene expression following transplantation. The nonhomogeneous distribution of plasmid vectors within the lung may be related to the animal model as well as the technique used for intratracheal administration in this study. Recent advances in aerosolization techniques now enable efficient, uniform intrapulmonary delivery of a variety of cytotoxic chemotherapeutic agents, antibiotics, as well as cytokines. These techniques have been sufficiently refined for the delivery of plasmid and antisense oligonucleotides to respiratory epithelium. In all likelihood, utilization of these techniques would have resulted in more uniform distribution of plasmid vectors within the lung, particularly if evaluated in the context of a large animal model in which aerosolized drug delivery is more efficient. Clinical trials evaluating aerosolized administration of cytotoxic agents for the treatment of inoperable pulmonary neoplasms are currently underway at the National Cancer Institute as well as several other centers within the United States; in all likelihood, these preliminary trials will provide the basis for aerosolized delivery of a large variety of agents for the treatment and prevention of aerodigestive tract cancers. The delivery of cytokines which can ameliorate acute ischemia-reperfusion injury, or allograft rejection may be additional applications of aerosolization technology. Once properly formulated, aerosolized pharmacologic agents or oligonucleotides may prove to be far more efficacious than gene constructs delivered via naked plasmid, or viral vectors to respiratory epithelium. As with plasmid or viral delivery systems, the distribution of aerosolized drugs will depend on the severity of ventilatory abnormalities resulting from secretions and air trapping within the transplanted lung. Because these agents traffic across respiratory epithelium to interstitial lymphatics, drugs delivered via aerosolization techniques may simultaneously inhibit inflammatory processes occurring within the alveolar space, interstitium, and regional lymph nodes. Doctor D’Ovidio and colleagues have confirmed that gene transfer to the respiratory epithelium is inefficient, and influenced by cold preservation techniques. Their experiments are a step in the right direction, and demonstrate the future potential of local delivery of therapeutic agents for the prevention of ischemia-reperfusion and allograft rejection in clinical lung transplantation.

Aerosols for systemic delivery of macromolecules.

During the past 50 years, aerosol therapy with small molecules has become the mainstay for managing lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. During the past decade, a new therapeutic paradigm has evolved-the delivery of macromolecules into the systemic circulation through the lung. Systemic pulmonary therapy with proteins and peptides resulted from major developments in dry powder drug formulations and aerosol delivery technology. These new technologies will enable the treatment of systemic disease, such as diabetes mellitus, noninvasively by means of the deep lung. Within a decade, it is likely that many medications will be administered in this way.

Flow structures and particle deposition patterns in double-bifurcation airway models. Part 1. Air flow fields

The understanding and quantitative assessment of air flow fields and local micron-particle wall concentrations in tracheobronchial airways are very important for estimating the health risks of inhaled particulate pollutants, developing algebraic transfer functions of global lung deposition models used in dose-response analyses, and/or determining proper drug-aerosol delivery to target sites in the lung. In this paper (Part 1) the theory, model geometries, and air flow results are provided. In a companion paper (Part 2, Comer et al. 2001), the history of particle deposition patterns and comparisons with measured data sets are reported. Decoupling of the naturally dilute particle suspension makes it feasible to present the results in two parts.Considering a Reynolds number range of 500 [les ] ReD [les ] 2000, it is assumed that the air flow is steady, incompressible and laminar and that the tubular double bifurcations, i.e. Weibel's generations G3–G5, are three-dimensional, rigid, and smooth with rounded as well as sharp carinal ridges for symmetric planar, and just rounded carinas for 90° non-planar configurations. The employed finite-volume code CFX (AEA Technology) and its user-enhanced FORTRAN programs were validated with experimental velocity data points for a single bifurcation. The resulting air flow structures are analysed for relatively low (ReD = 500) and high (ReD = 2000) Reynolds numbers. Sequential pressure drops due to viscous effects were calculated and compared, extending a method proposed by Pedley et al. (1977). Such detailed results for bifurcating lung airways are most useful in the development of global algebraic lung models.

Flow Structure and Particle Transport in a Triple Bifurcation Airway Model1

Considering steady laminar incompressible flow in a triple bifurcation, which represents generations three to six of the human respiratory system, air flow fields and micron-particle transport have been simulated for several combinations of relatively high and low inlet Reynolds and Stokes numbers. While the upstream bifurcations are hardly affected by the third bifurcation, complex air and particle flow fields occur in the daughter tubes leading to the third dividers. Variations in Reynolds number, 500⩽Re⩽2000, and Stokes number, 0.04⩽St⩽0.12, cause locally changing vortical air flows as well as irregular particle motions. Preferential concentration of particles can be induced by the secondary vortical flow in the tubes when the inlet Reynolds number is high enough. The air and particle velocity profiles in the third daughter tubes are still quite different from those in the upstream tubes, which indicates that additional downstream effects are possible. This work may contribute to respiratory dose estimation in health risk assessment studies, as well as the analyses of drug aerosol delivery.

Drugs used in the treatment of asthma: a review of clinical pharmacology and aerosol drug delivery.

The selection and titration of pharmacologic agents are essential in the treatment of asthma. This Article focuses on the primary medications used in the treatment of reactive airway disease. The recent advances in the technology of devices used to administer aerosolized medications are also reviewed.

Asthma medications and how to use them.

Aerosolized medications for the treatment of asthma are now considered to be the delivery system of choice. Despite their popularity, traditional pressurized metered dose inhalers are associated with a variety of drawbacks. This article reviews the aerosolized drug delivery systems currently available, along with their advantages and disadvantages. Patient technique in the use of these agents is addressed. Special considerations in children and the elderly are discussed, with specific recommendations tailored to these age groups, followed by practical suggestions for general inhaler use.

Drug delivery: A key factor in realising the full therapeutic potential of drugs

Drug delivery is a key factor contributing to the commercial and therapeutic potential of many drugs and related products. Drug delivery underpins the development of new chemical entities, and it is the driving force behind the development of many new devices and formulation-based projects. There are many exciting drug delivery projects being undertaken in commercial organisations, universities and research institutes throughout Australia. This article describes projects in the field of lipids and oral drug delivery, protein formulation and stability, aerosol drug delivery and transdermal drug delivery which are being undertaken in the authors' laboratories. It is hoped that these projects provide some insight into the scope and breadth of drug delivery research being conducted in “The Antipodes.” Drug Dev. Res. 46:316–327, 1999. © 1999 Wiley-Liss, Inc.

The Current Laboratory Determination of "Respirable Mass" Is Not Clinically Relevant

Journal of Aerosol MedicineVol. 11, No. s1 International Society for Aerosols in Medicine Focus Symposium TOWARDS MEANINGFUL LABORATORY TESTS FOR EVALUATION OF PHARMACEUTICAL AEROSOLS Puerto Rico, January 29–31,1997The Current Laboratory Determination of "Respirable Mass" Is Not Clinically RelevantMICHAEL T. NEWHOUSEMICHAEL T. NEWHOUSESearch for more papers by this authorPublished Online:25 Mar 2010https://doi.org/10.1089/jam.1998.11.Suppl_1.S-122AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byEffect of pressures and type of ventilation on aerosol delivery to chronic obstructive pulmonary disease patients15 April 2022 | Beni-Suef University Journal of Basic and Applied Sciences, Vol. 11, No. 1Fine Particle Fraction: The Good and the Bad Stephen P. Newman14 February 2022 | Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 35, No. 1Influences of Cannula Size and Flow Rate on Aerosol Drug Delivery Through the Vapotherm Humidified High-Flow Nasal Cannula SystemPediatric Critical Care Medicine, Vol. 14, No. 5Applying the AIM Concept in Support of Developing Improved In Vitro–In Vivo Relationships for OIPs25 February 2013Design of Facemasks for Delivery of Aerosol-Based Medication via Pressurized Metered Dose Inhaler with Valved Holding Chamber: Key Issues that Affect Performance R.W. Morton and J.P. Mitchell5 April 2007 | Journal of Aerosol Medicine, Vol. 20, No. s1Comparison of Three Valved Holding Chambers for the Delivery of Fluticasone Propionate–HFA to an Infant Face Model Emily Louca, Kitty Leung, Allan L. Coates, Jolyon P. Mitchell, and Mark W. Nagel23 June 2006 | Journal of Aerosol Medicine, Vol. 19, No. 2Cascade Impactors for the Size Characterization of Aerosols from Medical Inhalers: Their Uses and Limitations Jolyon P. Mitchell and Mark W. Nagel7 July 2004 | Journal of Aerosol Medicine, Vol. 16, No. 4Lung Deposition and Systemic Availability of Fluticasone Diskus and Budesonide Turbuhaler in ChildrenAmerican Journal of Respiratory and Critical Care Medicine, Vol. 168, No. 7Assessment of Comparative Bioequivalence of Two Metered-Dose Inhaler Formulations of SalbutamolClinical Drug Investigation, Vol. 22, No. 7Aerosols and Anti-Infectious Agents P. Diot, P.F. Dequin, B. Rivoire, F. Gagnadoux, F. Faurisson, E. Diot, E. Boissinot, A. Le Pape, L. Palmer, and E. Lemarié7 July 2004 | Journal of Aerosol Medicine, Vol. 14, No. 1Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 μ g day−1) versus HFA-fluticasone propionate (1000 μ g day−1) in patients with asthmaRespiratory Medicine, Vol. 95, No. 3Optimizing Drug Delivery to the Lung: Design of a CFC-Free Corticosteroid Metered-Dose Aerosol System22 February 2001 | Drug Development and Industrial Pharmacy, Vol. 27, No. 2Targets for inhaled treatmentRespiratory Medicine, Vol. 94An overview of the clinical efficacy of HFA-BDP in asthmaRespiratory Medicine, Vol. 94Transition to CFC-free metered dose inhalers — into the new millenniumInternational Journal of Pharmaceutics, Vol. 201, No. 1Dry Powder versus Intravenous and Nebulized Gentamicin in Cystic Fibrosis and BronchiectasisAmerican Journal of Respiratory and Critical Care Medicine, Vol. 160, No. 5 Volume 11Issue s1Jun 1998 To cite this article:MICHAEL T. NEWHOUSE.The Current Laboratory Determination of "Respirable Mass" Is Not Clinically Relevant.Journal of Aerosol Medicine.Jun 1998.S-122-S-132.http://doi.org/10.1089/jam.1998.11.Suppl_1.S-122Published in Volume: 11 Issue s1: March 25, 2010PDF download

Liquid drug aerosol delivery: whose responsibility?

Nebulisers require regular maintenance and may not be cost effective. But when they are used, it is essential community nurses give correct and consistent advice. Rachel Booker outlines the issues