Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"New Generation Nebulizers.","authors":"Martin Knoch","doi":"10.1089/jamp.2024.29116.mk","DOIUrl":"10.1089/jamp.2024.29116.mk","url":null,"abstract":"<p><p>Standard nebulizers are intended for general purpose use and typically are continuously operated jet or ultrasonic nebulizers. Evolutionary developments such as breath-enhanced and breath-triggered devices have improved delivery efficiency and ease of use, yet are still suitable for delivery of nebulized medications approved in this category. However, recent developments of vibrating membrane or mesh nebulizers have given rise to a significant increase in delivery efficiency requiring reformulation of former drug products or development of new formulations to match the enhanced delivery characteristics of these new devices. In addition, the electronic nature of the new devices enables tailoring to specific applications and patient groups, such as guiding or facilitating optimal breathing and improving adherence to the therapeutic regimen. Addressing these patient needs leads to new nebulization technologies being embedded in devices with fundamentally distinct functionality, modes of operation and patient interfaces. Therefore, new generation nebulizers can no longer be regarded as one category with fairly similar performance characteristics but must be clinically tested and approved as drug/device combinations together with the specific drug formulation, similar to the approval of pressurized metered-dose inhalers and dry powder inhalers. From a regulatory viewpoint, it is required that drug and device are associated with each other as combinations by clear, mutually conforming labels or, even more desirably, by distinct container-closure systems (closed system nebulizer).</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"157-165"},"PeriodicalIF":2.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nebulizers.","authors":"James B Fink, Kevin W Stapleton","doi":"10.1089/jamp.2024.29110.jbf","DOIUrl":"10.1089/jamp.2024.29110.jbf","url":null,"abstract":"<p><p>Nebulizers generate aerosols from liquid-based solutions and suspensions. Nebulizers are particularly well suited to delivering larger doses of medication than is practical with inhalers and are used with a broad range of liquid formulations. When the same drug is available in liquid or inhaler form, nebulizers are applicable for use with patients who will not or cannot reliably use a pressurized metered-dosed inhaler (pMDI) or dry powder inhaler (DPI) due to poor lung function, hand-breath coordination, cognitive abilities (e.g., infants, elderly) or device preference. In a nebulizer, liquid medication is placed in a reservoir and fed to an aerosol generator to produce the droplets. A series of tubes and channels direct the aerosol to the patient via an interface such as mouthpiece, mask, tent, nasal prongs or artificial airway. All nebulizers contain these basic parts, although the technology and design used can vary widely and can result in significant difference in ergonomics, directions for use, and performance. While many types of nebulizers have been described, the three categories of modern clinical nebulizers include: (1) pneumatic jet nebulizers (JN); (2) ultrasonic nebulizers (USN); and (3) vibrating mesh nebulizers (VMN). Nebulizers are also described in terms of their reservoir size. Small volume nebulizers (SVNs), most commonly used for medical aerosol therapy, can hold 5 to 20 mL of medication and may be jet, ultrasonic, or mesh nebulizers. Large volume nebulizers, typically jet or ultrasonic nebulizers, hold up to 200 mL and may be used for either bland aerosol therapy or continuous drug administration.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"140-156"},"PeriodicalIF":2.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying Exhaled Particles in Healthy Humans During Various Respiratory Activities Under Realistic Conditions.","authors":"Katharina Schwarz, Nadja Struß, Liudmila Banari, Jens M Hohlfeld","doi":"10.1089/jamp.2022.0076","DOIUrl":"10.1089/jamp.2022.0076","url":null,"abstract":"<p><p><b><i>Background:</i></b> Quantitatively collecting and characterizing exhaled aerosols is vital for infection risk assessment, but the entire droplet size spectrum has often been neglected. We analyzed particle number and size distribution of healthy participants in various respiratory activities, considering inter-individual variability, and deployed a simplified far-field model to inform on infection risks. <b><i>Methods:</i></b> Participants repeated the same respiratory activities on two visits. Particles were collected using an airtight extraction helmet supplied with High Efficiency Particulate Air (HEPA) filtered air. The sampling volume flow was transported to two particle counters covering the small and large particle spectrum. The applied simple mass balance model included respiratory activity, viral load, room size, and air exchange rates. <b><i>Results:</i></b> Thirty participants completed the study. The major fraction of the number-based size distribution was <5 μm in all respiratory activities. In contrast, the major fraction of the volume-based size distribution was 2-12 μm in tidal breathing, but >60 μm in all other activities. Aerosol volume flow was lowest in tidal breathing, 10-fold higher in quiet/normal speaking, deep breathing, coughing, and 100-fold higher in loud speaking/singing. Intra-individual reproducibility was high. Between participants, aerosol volume flow varied by two orders of magnitude in droplets <80 μm, and three orders of magnitude in droplets >80 μm. Simple model calculations not accounting for potential particle size-dependent differences in viral load and infection-related differences were used to model airborne pathogen concentrations. <b><i>Conclusions:</i></b> Quantitative analysis of exhaled aerosols for the entire droplet size spectrum as well as the variability in aerosol emission between individuals provides information that can support infection research. Clinical Trial Registration number: NCT04771585.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"51-63"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertonic Aerosols Hydrate Airways Longer and Reduce Acidification Risk with Nonpermeating Cation and Permeating Anion Salts.","authors":"Ana Flavia Zuim, Aurélie Edwards, Dennis Ausiello, Deen Bhatta, David A Edwards","doi":"10.1089/jamp.2023.0039","DOIUrl":"10.1089/jamp.2023.0039","url":null,"abstract":"<p><p><b><i>Background:</i></b> Hyperosmolar aerosols appear to promote or suppress upper airway dysfunction caused by dehydration in a composition-dependent manner. We sought to explore this composition dependence experimentally, in an interventional human clinical study, and theoretically, by numerical analysis of upper airway ion and water transport. <b><i>Methods:</i></b> In a double-blinded, placebo-controlled clinical study, phonation threshold pressure (PTP) was measured prenasal and postnasal inhalation of hypertonic aerosols of NaCl, KCl, CaCl₂, and MgCl₂ in seven human subjects. Numerical analysis of water and solute exchanges in the upper airways following deposition of these same aerosols was performed using a mathematical model previously described in the literature. <b><i>Results:</i></b> PTP decreased by 9%-22% relative to baseline (<i>p</i> < 0.05) for all salts within the first 30 minutes postadministration, indicating effective laryngeal hydration. Only MgCl₂ reduced PTP beyond 90 minutes (21% below baseline at 2 hours postadministration). By numerical analysis, we determined that, while airway water volume up to 15 minutes postdeposition is dictated by osmolarity, after 30 minutes, divalent cation salts, such as MgCl₂, better retain airway surface liquid (ASL) volume by slow paracellular clearance of the divalent cation. Fall of CFTR chloride flux with rise in ASL height, a promoter of airway acidification, appears to be a signature of permeating cation (NaCl) and nonpermeating anion (mannitol) aerosol deposition. For hypertonic aerosols that lack permeating cation and include permeating anion (CaCl₂ and MgCl₂), this acid-trigger signature does not exist. <b><i>Conclusions:</i></b> Nonpermeating cation and permeating anion hypertonic aerosols appear to hydrate upper airways longer and, rather than provoke, may reduce laryngeal dysfunction such as cough and bronchoconstriction.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"64-76"},"PeriodicalIF":2.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical Considerations in Dose Extrapolation from Animals to Humans.","authors":"Anthony J Hickey, Sara E Maloney, Phillip J Kuehl, Jonathan E Phillips, Ronald K Wolff","doi":"10.1089/jamp.2023.0041","DOIUrl":"10.1089/jamp.2023.0041","url":null,"abstract":"<p><p>Animal studies are an important component of drug product development and the regulatory review process since modern practices have been in place, for almost a century. A variety of experimental systems are available to generate aerosols for delivery to animals in both liquid and solid forms. The extrapolation of deposited dose in the lungs from laboratory animals to humans is challenging because of genetic, anatomical, physiological, pharmacological, and other biological differences between species. Inhaled drug delivery extrapolation requires scrutiny as the aerodynamic behavior, and its role in lung deposition is influenced not only by the properties of the drug aerosol but also by the anatomy and pulmonary function of the species in which it is being evaluated. Sources of variability between species include the formulation, delivery system, and species-specific biological factors. It is important to acknowledge the underlying variables that contribute to estimates of dose scaling between species.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"77-89"},"PeriodicalIF":2.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dr. Michael Newhouse (March 21, 1935-December 25, 2023), a Global Legacy in Respiratory Medicine and Aerosol Therapy, My Mentor.","authors":"Israel Amirav","doi":"10.1089/jamp.2024.29114.mem","DOIUrl":"10.1089/jamp.2024.29114.mem","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"111-112"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerosolizable Pyrazinamide-Loaded Biodegradable Nanoparticles for the Management of Pulmonary Tuberculosis.","authors":"Komal Parmar, Swati Sondarva","doi":"10.1089/jamp.2022.0078","DOIUrl":"10.1089/jamp.2022.0078","url":null,"abstract":"<p><p><b><i>Background:</i></b> Pyrazinamide is a Biopharmaceutical Classification System class III antibiotic indicated for active tuberculosis. <b><i>Methods:</i></b> In the present work, pyrazinamide-loaded biodegradable polymeric nanoparticles (PNPs) based dry powder inhaler were developed using the double emulsion solvent evaporation technique and optimized using design of experiments to provide direct pulmonary administration with minimal side effects. Batches were characterized for various physicochemical and aerosol performance properties. <b><i>Results:</i></b> Optimized batch exhibited particle size of 284.5 nm, % entrapment efficiency of 71.82%, polydispersibility index of 0.487, zeta potential of -17.23 mV, and <i>in vitro</i> drug release at 4 hours of 79.01%. Spray-dried PNPs were evaluated for drug content, <i>in vitro</i> drug release, and kinetics. The particle mass median aerodynamic diameter was within the alveolar region's range (2.910 μm). In the trachea and lung, there was a 2.5- and 1.2-fold increase in <i>in vivo</i> deposition with respect to pure drug deposition, respectively. <i>In vitro</i> drug uptake findings showed that alveolar macrophages with pyrazinamide PNPs had a considerably higher drug concentration. Furthermore, accelerated stability studies were carried out for the optimized batch. Results indicated no significant change in the evaluation parameters, which showed stability of the formulation for at least a 6-month period. <b><i>Conclusion:</i></b> PNPs prepared using biodegradable polymers exhibited efficient pulmonary drug delivery with decent stability.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"30-40"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acceptance Testing of Used Cascade Impactor Stages Based on Pressure Drop Measurements in a Flow System Managed with a Critical Flow Venturi: Part I-Laboratory Proof-of-Principle.","authors":"Daryl L Roberts","doi":"10.1089/jamp.2023.0035","DOIUrl":"10.1089/jamp.2023.0035","url":null,"abstract":"<p><p><b><i>Background:</i></b> Cascade impactors are essential for measuring the aerodynamic particle size distribution delivered by metered dose, dry powder, and similar inhalable drug products. For quality control of used impactors, periodic optical inspection of the nozzles of each impactor stage (stage mensuration) is currently the only method sufficiently precise to test whether used impactors are suitable for continued use, in accord with pharmacopeial standards. Here, we demonstrate a new method for quality control of used impactors. The method combines stage-wise pressure-drop measurement with a critical flow venturi (CFV) for air flow management. This technique avoids the unacceptably large uncertainty in conventional air flow rate measurements and instead relies on pressure and temperature measurement upstream of the CFV. These measurements can be made precisely with affordable equipment. <b><i>Methods:</i></b> We placed a toroidally shaped CFV downstream of a Next Generation Impactor™** (NGI) and precisely measured the stagnation pressure (±0.02%) and temperature (±0.03%) upstream of this CFV at impactor inlet flow rates close to 60 L/min. Pressure-drop measurements (±0.25%) at stages 3-7 and the micro-orifice collector were made with capacitive diaphragm transducers and with a special lid to the NGI that allowed pneumatic connection to the interstage passageways before and after each impactor stage. <b><i>Results:</i></b> The measured pressure drop values matched, to fractional percentage precision, those predicted by the incompressible flow theory through the nozzles and the compressible flow theory through the CFV. <b><i>Conclusions:</i></b> Practical equipment has been assembled that measures, to fractional percentage precision, the pressure drop through impactor nozzles at precisely managed flow conditions. The experimental results support the relevant flow principles. The results, thereby, support the use of this method for quantifying whether used impactor stages are suitable for continued use in the testing of registered inhalable drug products, in accord with pharmacopeial standards.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"2-10"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling.","authors":"Neil A Miller","doi":"10.1089/jamp.2023.29100.nam","DOIUrl":"10.1089/jamp.2023.29100.nam","url":null,"abstract":"<p><p>Modeling is coming to the fore as it is now widely accepted and indeed expected during drug discovery and development. Modeling integrates knowledge, increases understanding and provides the ability to predict an outcome either before it occurs or when it is not possible to measure. This makes modeling an attractive option for inhaled drugs as it is not possible to routinely measure what is occurring to the drug (pharmacokinetics) and what effect the drug is having (pharmacodynamics) at local microscopic sites of such a diverse and complex organ as the lung. Many pieces of information (data and knowledge) exist like the pieces of a jigsaw puzzle and modeling brings the pieces together in a scientific and mechanistically coherent manner to increase understanding of both the efficacy and safety of inhaled drugs.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"41-49"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgment of Reviewers 2023.","authors":"","doi":"10.1089/jamp.2024.29106.ack","DOIUrl":"10.1089/jamp.2024.29106.ack","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"37 1","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139712246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}