Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Advances in the Application of Additive Manufacturing in Respiratory Inhalation Therapy.","authors":"Chao Zhang, Xinyu Zhang, Junhui Zhang, Changhong Huo","doi":"10.1177/19412711261442505","DOIUrl":"10.1177/19412711261442505","url":null,"abstract":"<p><p>Inhalation therapy has become a cornerstone in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, owing to its rapid onset, direct pulmonary targeting, and avoidance of first-pass metabolism. Its clinical scope has expanded beyond conventional respiratory indications to emerging applications, including vaccine delivery, systemic disease management, and localized tumor therapy. However, traditional inhalation systems are often designed for the average patient, overlooking physiological variability that results in inconsistent drug deposition and therapeutic efficacy-particularly in children, elderly patients, and individuals with airway abnormalities. Additive manufacturing (AM), with its high design flexibility and capacity for personalization, offers new possibilities for structural optimization, particle engineering, and <i>in vitro</i> model fabrication in inhalation therapy. Growing evidence indicates that 3D-printed inhalation devices and formulation platforms can enhance drug deposition control, patient compliance, and delivery precision. This review provides a comprehensive overview of recent advances in AM applied to inhalation therapy, highlighting its roles in personalized device fabrication, microdose particle design, and <i>in vitro</i> model construction, as well as in the exploration of emerging therapeutic strategies. Furthermore, it discusses current technical challenges and translational barriers. Overall, AM is propelling the transition of inhalation therapy from standardized approaches toward intelligent, patient-centered delivery systems, offering both theoretical and technological foundations for next-generation respiratory healthcare.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"236-248"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690175","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":"Integrating <i>In Vitro</i> Performance and <i>In Vivo</i> Patient-Reported Outcomes of a Mometasone Furoate Nasal Spray Device: A Translational Evaluation.","authors":"Alessandra Sorano, Virginia Patterlini, Fabio Sonvico, Giulia Fabietti, Ludovica Benuzzi, Giorgio Vitale, Federico Lavorini, Francesca Buttini","doi":"10.1177/19412711261420781","DOIUrl":"10.1177/19412711261420781","url":null,"abstract":"<p><strong>Background: </strong>Intranasal corticosteroids (INCSs) are widely prescribed for allergic and nonallergic rhinitis and chronic rhinosinusitis, frequent causes of upper airway cough syndrome (UACS). In UACS, adherence is strongly influenced not only on pharmacological efficacy but also on device performance and sensory tolerability. Despite this, few studies have linked <i>in vitro</i> spray characteristics with patient-reported outcomes.</p><p><strong>Objective: </strong>To evaluate the technological characteristics and clinical acceptability of mometasone furoate administered via the liquid VP3 nasal spray device by integrating <i>in vitro</i> performance testing and <i>in vivo</i> patient-reported outcomes in individuals with chronic cough and UACS.</p><p><strong>Methods: </strong><i>In vitro</i> experiments assessed deposition patterns in a silicone nasal cast, dripping behavior on inclined gel surfaces, viscosity, and spray plume geometry. An observational study enrolled 10 patients (80% female, mean age 56 ± 8.4 years) referred to a tertiary cough clinic for chronic cough (mean duration 3.5 years) associated with postnasal drip. Patients switched from conventional mometasone sprays to the device and completed Anchored Best-Worst Scaling evaluations of 11 sensory and treatment-related attributes. Global satisfaction was rated using a visual analog scale (VAS) and Treatment Satisfaction Index (TSI).</p><p><strong>Results: </strong>Deposition was reproducible (27.9 ± 1.7% of cast surface) with distribution into middle and lower turbinates. Moderate viscosity (14.4 ± 3.2 mPa·s) and stable plume geometry supported retention. <i>In vivo</i>, overall satisfaction scores remained stable following switching (TSI: 64.3 ± 3.4 vs 63.8 ± 4.6; VAS: 6.8 ± 3.2 vs 6.1 ± 1.6). However, patients reported significantly greater satisfaction in two sensory domains and rated three domains as more important (<i>p</i> < 0.05). No deterioration in any attribute was observed.</p><p><strong>Conclusion: </strong>The liquid VP3 nasal spray device delivering mometasone furoate demonstrated reliable <i>in vitro</i> performance and favorable patient acceptability in UACS. The correspondence between deposition behavior and patient-reported tolerability supports its suitability for INCS delivery and warrants further evaluation in larger, longer-term studies.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"213-220"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118989","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":"Flow Control When Testing Dry-Powder Inhalers.","authors":"Daryl L Roberts","doi":"10.1177/19412711261448446","DOIUrl":"10.1177/19412711261448446","url":null,"abstract":"<p><strong>Background: </strong>International compendia specify setting the flow for testing dry powder inhalers (DPIs) with the pressure ratio across the flow control valve ≤0.5. This guidance derives from thermodynamic theory, but there is no requirement that the flow control equipment demonstrates adherence to this theory. There is therefore a need to define and test for acceptable flow control valve performance, enabling DPI manufacturers to determine whether their test equipment is achieving the expected flow control. Herein, we present flow control data for two valves common in the inhaler testing community and describe the need for qualification specifications for flow control equipment with such valves.</p><p><strong>Methods: </strong>We devised a simple laboratory apparatus and method for determining the mass flow rate through two common flow control valves in their commercial configuration. In the test method, the pressure ratio across the valve is lowered from ∼0.7 to 0.3. This range of pressure ratio covers the standard test requirement that the pressure ratio must be 0.5 or less and maps the transition of compressible flow through the valve to the point where the air flow theoretically remains constant.</p><p><strong>Results: </strong>A common industrial valve, mentioned specifically in Pharm. Eur. 2.9.18 and in earlier editions of United States Pharmacopeia 601, exhibits nearly constant flow when the pressure ratio is <0.5. Another valve in widespread use exhibits a continued slight increase in mass flow rate even as the pressure ratio is decreased below 0.5.</p><p><strong>Conclusions: </strong>Inhaler testing laboratories should test whether their equipment exhibits the constant flow condition that is often assumed when the pressure ratio across the flow control valve is 0.5 or smaller. Quantitative specifications, yet to be developed, for qualifying commercial flow control equipment must account for both the transient start-up and the steady-state flow in DPI testing.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"228-235"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838154","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":"Digital Image Segmentation Analysis Enables High-Throughput Next-Generation Impactor Analysis.","authors":"Jaston McClure, Daniel Dobson, Ed Yost, Derek M Dalton, Marcelino Varona","doi":"10.1177/19412711261436539","DOIUrl":"10.1177/19412711261436539","url":null,"abstract":"<p><p><i>Purpose:</i> Aerodynamic particle size distribution (APSD) determination is a key quality attribute for inhaled therapeutics. The next-generation impactor is the gold standard for APSD determination; however, it suffers from lengthy analysis times due to the need for high-performance liquid chromatography (HPLC)-based quantitation. In this work, a novel method employing image analysis is developed to derive APSD metrics from dry powder inhalers.<i>Major Findings:</i> Analysis of neat active pharmaceutical ingredient (API), API/lactose blends, and stressed blend samples is demonstrated. The method shows sufficient resolution to differentiate between different sizes of neat API and within lactose blends. In addition, the results obtained from image analysis are comparable to the HPLC derived results.<i>Conclusions:</i> This study establishes the feasibility of image analysis for faster APSD determination.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"221-227"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574092","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":"Effect of Nebulizer Breath-Guiding on Breathing Patterns and Lung Deposition.","authors":"Benjamin Heine, Uwe Schuschnig, Jakob Richter, Andreas Liebl, Lea Botermann, Gesa Bräunlich, Nicolas Schwenck, Maximilian J Grill, Michael Hahn","doi":"10.1177/19412711261488960","DOIUrl":"https://doi.org/10.1177/19412711261488960","url":null,"abstract":"<p><strong>Background: </strong>Efficient aerosol therapy depends on both device performance and inhalation technique. Breath-triggered vibrating mesh nebulizers reduce drug loss by generating aerosol only during inspiration but may prolong treatment. Guiding patients toward slow, deep breathing could improve lung deposition and shorten nebulization time, yet quantitative evidence, particularly across disease groups, remains limited.</p><p><strong>Objective: </strong>To assess how integrated breath-guiding features influence breathing behavior, lung deposition, and user perception in healthy adults and in patients with obstructive or restrictive lung disease.</p><p><strong>Methods: </strong>Sixty-four participants inhaled through three nebulizer configurations: a low-resistance reference (eFlow OS) and two versions of the eFlow Integrated featuring direction-dependent resistance and multimodal feedback, tested with or without a breath-guiding app. Flow signals from multiple breaths were analyzed to determine phase-averaged breathing parameters. Device effects were evaluated by ANOVA. Representative breathing patterns and unsteady aerosol characteristics were input to a validated whole-lung <i>in silico</i> model to estimate deposition. User experience was assessed by questionnaire.</p><p><strong>Results: </strong>Breath-guiding consistently altered inhalation behavior. Peak inspiratory flow decreased by ∼20%, the I/E ratio increased by >15%, and with the breath guide app, tidal volume (+40%) and breath duration (+47%) increased. These effects were similar across disease groups. <i>In silico</i> simulations showed improved delivery with guided inhalation: lung drug deposition rate increased by 3.7% and 15.5%, and alveolar deposited mass fraction rose by 66% and 76% versus the reference. The breath guide app further shifted deposition from extrathoracic to thoracic and alveolar regions and reduced exhalation losses (-14%). Most participants (88%) were satisfied or very satisfied, citing pleasant resistance and helpful app guidance.</p><p><strong>Conclusion: </strong>Breath-guiding features and digital coaching reliably promote slower, deeper breathing, leading to greater lung and alveolar deposition and shorter expected nebulization times. High user acceptance underscores the clinical potential of patient-centric, guided inhalation in optimizing aerosol therapy.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261488960"},"PeriodicalIF":2.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081029","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":"The Impact of Inspiratory Muscle Function on Inhaler Device Adaptability in Stable COPD Patients.","authors":"Yanwen Zheng, Jing Wang, Haiyan Wu","doi":"10.1177/19412711261490198","DOIUrl":"https://doi.org/10.1177/19412711261490198","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the relationship between inspiratory muscle function and inhaler device adaptability in stable chronic obstructive pulmonary disease (COPD) patients, addressing the gaps in objective evaluation methods for inhaler device effectiveness in clinical practice.</p><p><strong>Methods: </strong>A cross-sectional study of 701 stable COPD patients (498 males, 203 females; aged 48-83 years) from the First People's Hospital of Xiaoshan District was conducted from June 2023 to May 2024. Maximum inspiratory pressure (MIP) measured respiratory muscle function, while average effective inspiratory flow assessed inhaler adaptability. Participants used either dry powder inhalers (DPI) or pressurized metered-dose inhalers/soft mist inhalers (pMDI/SMI). Multiple regression models adjusted for demographic and respiratory parameters.</p><p><strong>Results: </strong>Higher MIP quartiles correlated with increased average effective inspiratory flow (Q4 vs. Q1: β = 8.1 L/min, 95% CI: 5.1-11.0, <i>p</i> < 0.001) after adjusting for demographic factors. This association diminished after controlling for respiratory parameters, suggesting MIP indirectly affects inhaler adaptability through intermediate respiratory metrics. A potential threshold effect was identified at MIP of 23.1 cmH₂O, though not statistically significant (<i>p</i> = 0.208).</p><p><strong>Conclusion: </strong>Our study demonstrates that inspiratory muscle function, as assessed by MIP, is significantly associated with measures of inhaler device adaptability, and identifies a physiologically relevant threshold range that may help characterize patient requirements for inhalers of differing resistance.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261490198"},"PeriodicalIF":2.2,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061245","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":"<i>Letter:</i> Falsification of the sPIFR Hypothesis.","authors":"Jeffry G Weers, Thomas E Tarara, Danforth P Miller","doi":"10.1177/19412711261481901","DOIUrl":"10.1177/19412711261481901","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261481901"},"PeriodicalIF":2.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968806","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":"Evaluating Powder Deposition in the Nasal Airways Using a Facile Fluorescent-Imaging Method.","authors":"William Hunter, Kiao Inthavong, Sara Vahaji, Svetlana Stevanovic, David Morton","doi":"10.1177/19412711261477975","DOIUrl":"https://doi.org/10.1177/19412711261477975","url":null,"abstract":"<p><p><i>Background:</i> Intranasal drug delivery is a critical route for both systemic and targeted therapies, particularly for drugs intended to reach the central nervous system via the olfactory region. However, current aqueous nasal sprays have limited penetration beyond the anterior nasal airway, reducing their efficacy for nose-to-brain drug delivery. Nasal powder insufflators offer a promising alternative, as they allow higher drug payloads, typically up to 50 mg. The narrower spray cone angle of some powder insufflators has the potential for improved drug penetration, making them more suitable to deliver drugs higher and deeper into the nasal airways than is possible for aqueous nasal sprays. Despite this potential, existing methods for assessing powder deposition rely on complex and expensive imaging techniques such as gamma scintigraphy or MRI, limiting their accessibility for formulation and device optimization.<i>Methods:</i> This study presents a novel, cost-effective fluorescent imaging method to evaluate nasal powder deposition patterns using a transparent Koken nasal cast coated with synthetic mucus. Fluorescein-dyed spray-dried powders were delivered through a capsule-based nasal powder insufflator actuated by an air pulse, and deposition patterns were visualized under UV excitation. ImageJ analysis was used to quantify fluorescent intensity and distribution across five predefined nasal regions.<i>Results:</i> The results demonstrated that the powder delivery device successfully bypassed the anterior nasal airway and deposited a significant proportion of the dose in the olfactory region, achieving a mean posterior upper airway deposition of 51.7%, a substantial improvement over conventional aqueous sprays. The air pulse-actuated delivery mechanism also exhibited high repeatability, with a coefficient of variation of 14.9% in olfactory region deposition.<i>Conclusion:</i> By providing a simple, noninvasive alternative to radiolabeled imaging, this fluorescence-based approach enables rapid evaluation of nasal powder formulations and delivery devices. Hence, the approach described in this work could enable the nasal delivery device parameters, and powder formulation parameters to be optimized for nasal powder delivery devices. This could in turn allow drug delivery efficiency to different regions of the nose-particularly the upper nasal airways-to be optimized to suit different powder formulations, and different powder delivery devices.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261477975"},"PeriodicalIF":2.2,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764957","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":"Preclinical Development of a Dry Powder Formulation of Loxapine for Intranasal Delivery.","authors":"Paul Shields, Irene Rossi, Daniela Schwotzer, Philip J Kuehl, Lucas Silva, Julie D Suman","doi":"10.1177/19412711261470959","DOIUrl":"https://doi.org/10.1177/19412711261470959","url":null,"abstract":"<p><strong>Background: </strong>Acute agitation (AA) is a common symptom of psychiatric conditions such as bipolar disorder and schizophrenia, resulting in 1.7 million emergency room visits per year in the United States. Loxapine, administered by inhalation, is an approved treatment for such scenarios. A boxed warning for bronchospasm when administered via inhalation limits its use to inpatient settings, making effective treatment for AA in outpatient settings an unmet need. The objective of this study was to develop and identify a lead intranasal dry powder formulation for outpatient treatment of AA.</p><p><strong>Materials and methods: </strong>Seven spray-dried nasal powders (Formulations A-G) consisting of loxapine succinate (Medichem, ES) and various excipients were manufactured and filled in a Unidose Nasal Powder system (Aptar Pharma, FR). In this pharmacokinetic study with non-compartmental analysis, formulations were evaluated both <i>in vitro</i> and <i>in vivo</i> (<i>n</i> = 4 non-human primates [NHPs]). Formulations were characterized by yield, assay, water content, particle size distribution, emitted dose, and impactor-sized mass.</p><p><strong>Results: </strong>Formulation B, comprising mannitol and hypromellose with 30% loxapine by weight, was identified as the lead candidate. In the <i>in vivo</i> portion of the study, all formulations were well tolerated. The plasma versus time profile for the NHP study indicated that Formulation B achieved the greatest extent of absorption (203.9 ng/mL*h) compared to the intravenous (control) formulation (231.5 ng/mL*h), each administered as a 3 mg dose. The full pharmacokinetic results for all formulations showed similar rapid absorption following dosing, although the area under the concentration-time curve and maximum concentration were lower than those observed with Formulation B. All formulations had similar apparent terminal half-lives.</p><p><strong>Conclusions: </strong>Formulation B showed clear advantages both <i>in vitro</i> and <i>in vivo</i>, supporting its suitability for further development as an outpatient treatment for AA in schizophrenia and bipolar disorder.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261470959"},"PeriodicalIF":2.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689320","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":"<i>Letter:</i> Letter to the Editor In Response to Weers et al.","authors":"Roy Pleasants","doi":"10.1177/19412711261453165","DOIUrl":"10.1177/19412711261453165","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"207"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972789","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}