Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Preclinical Testing of a New Dry Powder Aerosol Synthetic Lung Surfactant Formulation and Device Combination for the Treatment of Neonatal Respiratory Distress Syndrome.","authors":"Worth Longest, Michael Hindle, Dale Farkas, Mohammad A M Momin, Caleb Dalton, Felicia Hall, Ghali Aladwani, Hattie KenKnight, Robert M DiBlasi","doi":"10.1089/jamp.2025.0001","DOIUrl":"https://doi.org/10.1089/jamp.2025.0001","url":null,"abstract":"<p><p><b><i>Background:</i></b> This study advanced the preclinical development of a new dry powder aerosol synthetic lung surfactant (SLS) product for neonatal respiratory distress syndrome (RDS) by integrating a multiple-actuation device and scalable spray-dried formulation, evaluating physicochemical and <i>in vitro</i> aerosol performance, and then comparing biological efficacy with the current clinical standard of high-volume liquid bolus instillation. <b><i>Methods:</i></b> A new high-dose air-jet dry powder inhaler was developed that was characterized by a variable-volume aerosolization chamber (D3 device) with the goal of unifying aerosol quality and emitted dose (ED) over multiple actuations. The SLS excipient enhanced growth dry powder formulation was advanced through production on a scalable nozzle-based spray dryer system (Mini Spray Dryer; MSD2 formulation). Physicochemical characterization of the formulation was performed along with <i>in vitro</i> aerosol testing of the new D3-MSD2 device and formulation combination. The optimized D3-MSD2 aerosol therapy was then evaluated in a rabbit model of severe RDS. <b><i>Results:</i></b> The new D3-MSD2 combination produced a small-particle aerosol with high fine particle fraction (FPF_{<5 µm} = 87.9%; FPF_{<2.5 µm} = 61.6%) and percent ED (77.4% of loaded). Additional <i>in vitro</i> testing highlighted consistent particle size (D_v50 = 1.6 µm) and ED across multiple actuations. In the animal model experiments, a total device-loaded formulation mass of 60 mg (delivered as 2x30 mg) produced a total phospholipid (PL) dose of 24 mg-PL/kg and a device ED of 18 mg-PL/kg compared with the 200 mg-PL/kg clinical dose of Curosurf liquid. <i>In vivo</i> response rate for the D3-MSD2 aerosol therapy was considerably more rapid with arterial oxygenation recovering 5-12 times faster than for liquid Curosurf. Biological response for the D3-MSD2 aerosol therapy was also superior with 2-fold improvement in final lung compliance compared with liquid Curosurf. <b><i>Conclusions:</i></b> The new D3-MSD2 aerosol therapy was found to be superior to clinical-practice liquid bolus instillation in the critical areas of required dose (order-of-magnitude reduction), delivery time, biological response rate, and efficacy.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965555","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":"Association of Inhaled Corticosteroid Use with COVID-19 Severity and Hospitalization in Patients With and Without Respiratory Disease.","authors":"Michal Leibovitch, Bernice Oberman, Jacob Cohen, Tamar Strahl, Noga Yosef, Yael Reichenberg, Dekel Shlomi","doi":"10.1089/jamp.2025.0004","DOIUrl":"https://doi.org/10.1089/jamp.2025.0004","url":null,"abstract":"<p><p><b><i>Background:</i></b> Several studies have demonstrated the benefit of inhaled corticosteroids (ICS) before COVID-19 illness in reducing hospitalization time and reducing viral entrance to lung cells. This study explores the risk of severe COVID-19 illness among patients who had purchased ICS. <b><i>Methods:</i></b> In a retrospective study, adult patients with COVID-19 before the emergence of the Omicron variant were included. The severity, hospitalization rates, and mortality due to COVID-19 among patients who purchased and did not purchase ICS during the 6 months before the illness were compared. <b><i>Results:</i></b> Of the 44,866 COVID-19 patients, 2359 (5.3%) were hospitalized. Information regarding the severity of hospitalization was available for 2259 patients. Of these, 602 (27%) were classified as having severe disease and 510 (22%) died. Patients with higher socioeconomic status (SES) had less hospitalization rates but significantly higher risk for severe COVID-19 and a higher mortality rate. In a multivariate analysis, a significantly higher risk for hospitalization was found only for patients who purchased ICS when no respiratory disease was recorded (odds ratio 1.53,95% confidence interval: 1.15-2.01), relative to those who did not purchase ICS. <b><i>Conclusions:</i></b> Patients with unrecorded respiratory disease who purchased ICS are at higher risk for hospitalization due to COVID-19; therefore, rigorous attempts should be made to better characterize their illness. Higher SES was associated with more severe COVID-19 and higher mortality rates and these patients should have early hospitalization.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017721","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":"Inhalable and Nasal Biologics: Analytical, Formulation, Development, and Regulatory Considerations.","authors":"David Cipolla, Christopher J Gruenloh, Nani Kadrichu, Philip J Kuehl, Lei Mao, Bing V Li, Svetlana Lyapustina, Heidi M Mansour, Franz-Josef K Rehmann, Irene Rossi, Gur Jai Pal Singh, Julie D Suman, Nurcin Ugur","doi":"10.1089/jamp.2024.0058","DOIUrl":"https://doi.org/10.1089/jamp.2024.0058","url":null,"abstract":"<p><p><b><i>Background:</i></b> Delivering large molecules and biologics via inhalation or intranasal routes allows these innovative therapies to directly target the respiratory tract, access the richly vascularized lymphatic tissue in the nose for vaccination, bypass gastro-intestinal and first-pass hepatic metabolism for systemically active drugs, and provide a convenient alternative to injections. These advantages are driving significant growth in research and development within this field. However, before such products can reach the market, they must undergo rigorous nonclinical studies and clinical trials and address challenges related to formulation, manufacturing, analytical testing, quality standards, and regulatory review. <b><i>Methods and Results:</i></b> This report summarizes discussions among leading experts from industry, academia, and regulatory bodies on how to apply general Chemistry, Manufacturing, and Controls (CMC) principles, alongside bioequivalence (BE) considerations, to the development of inhalable and nasal biologics (INBs). It also explores the balance between these requirements and the established techniques for medical aerosols. In the absence of explicit regulatory guidelines for the development of INBs, this article reviews applicable literature, including guidelines from the US FDA and EMA for biologics, on the one hand, and for small-molecule inhalation and nasal drug products, devices, and combination products, on the other. The original discussions reflected here took place at the 2023 workshop co-organized by the International Society for Aerosols in Medicine (ISAM) and the International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS). Subsequent recent developments have also been added. The article describes regulatory expectations, the selection of delivery systems and formulation types, and analytical techniques for assessing product quality attributes of INBs. Several specific cases are presented in detail, including regulatory considerations for generic peptides, the approval package for one of the first marketed biologics for inhalation, and analytical detection strategies for viral-based products delivered to the lungs. <b><i>Conclusions:</i></b> Looking ahead, the future of INBs includes opportunities to treat and potentially cure diseases that currently have no effective treatment or that require repeated injections. Continued collaboration among researchers, developers and regulators will be key to advancing these therapies, ultimately benefiting patients and improving health outcomes. The future of INBs looks promising!.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803553","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":"Scale-Up and Postapproval Changes in Orally Inhaled Drug Products: Scientific and Regulatory Considerations.","authors":"Gur Jai Pal Singh, S Prasad Peri","doi":"10.1089/jamp.2024.0036","DOIUrl":"10.1089/jamp.2024.0036","url":null,"abstract":"<p><p>Approved drug products may be subject to change(s) for a variety of reasons. The changes may include, but are not limited to, increase in batch size, alteration of the drug product constituent(s), improvement in the manufacturing process, and shift in manufacturing sites. The extent of pharmaceutical testing and the regulatory pathway for timely implementation of any change in the approved product and/or process depends upon the nature and extent of change. The U.S. Food and Drug Administration (FDA) has published guidelines that outline its expectations for the Scale-Up and Postapproval Changes (SUPAC) in the solid oral immediate and modified release (MR) products, and semisolid formulations. However, to date, no such guidelines have been issued to address SUPAC in the orally inhaled drug products (OIDPs), and this article represents a seminal contribution in this direction. It is hoped that it will inspire contributions from the relevant multidisciplinary experts from the pharmaceutical industry and the agency in accomplishing formal regulatory guidelines relevant to the OIDP SUPAC. The OIDPs are complex drug-device combination products. Therefore, a conceptualization of SUPAC guidelines for these products warrants consideration of contributions of effect of change(s) in individual components (drug substance, formulation, device) as well as a compound effect that a single or multiple changes may have on product performance, and its safety and efficacy. This article provides a discussion of scientific aspects and regulatory bases relevant to the development of SUPAC for OIDPs, and it attempts to outline considerations that may be applicable in addressing issues related to the OIDP SUPAC in the context of human drugs. The authors' statements should not be viewed as recommendations from any regulatory agency, as the applicable guidelines would be determined on case-by-case evaluation by the relevant authorities.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"39-63"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794600","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":"<i>In Vitro</i> Comparison of Inspiration-Synchronized and Continuous Vibrating Mesh Nebulizer During Adult Invasive Mechanical Ventilation.","authors":"Jie Li, Caylie A Sheridan, Osama Alanazi, James B Fink","doi":"10.1089/jamp.2024.0047","DOIUrl":"10.1089/jamp.2024.0047","url":null,"abstract":"<p><p><b><i>Background:</i></b> Aerosol delivery may be enhanced by utilizing an inspiration-synchronized nebulization mode, where nebulization occurs only during inspiration. This study aimed to compare aerosol delivery of albuterol via a prototype of an inspiration-synchronized vibrating mesh nebulizer (VMN) versus continuous VMN during invasive mechanical ventilation. <b><i>Methods:</i></b> A critical care ventilator equipped with a heated-wire circuit to deliver adult parameters was attached to an endotracheal tube (ETT), a collection filter, and a test lung. The nebulizer was placed at the humidifier's inlet, inspiratory limb at the Y-piece, and between the Y-piece and ETT. Conventional VMNs producing standard size aerosol particles (Solo; Aerogen Ltd) were compared with prototype small-particle VMNs (Aerogen Pharma) in both inspiration-synchronization and continuous modes. In each run, 1 mL of albuterol (2.5 mg) was used (<i>n</i> = 5). The drug was eluted from the collection filter and assayed with UV spectrophotometry (276 nm). <b><i>Results:</i></b> The inhaled dose with inspiration-synchronization mode was 1.4 to 3.6 times that with the continuous mode, regardless of nebulizer positions (all <i>p</i> < 0.001). The small-particle VMN delivered an 8%-69% greater inhaled dose than the conventional VMN (Solo), regardless of the nebulizer placement or aerosol generation mode (all <i>p</i> < 0.001). The highest inhaled dose (50%-60%) with the inspiration-synchronized VMN was observed when it was placed at the ETT (all <i>p</i> < 0.001), whereas the continuous VMN performed better when positioned near the humidifier, with an inhaled dose of 21%-37% (<i>p</i> < 0.001). <b><i>Conclusion:</i></b> The inspiration-synchronized VMN delivered a greater inhaled dose than continuous VMN, irrespective of nebulizer placement. The prototype VMN producing smaller aerosol particles resulted in a greater inhaled dose than the conventional VMN (Solo), regardless of placement or aerosol generation modes. The inspiration-synchronized VMN achieved the highest delivery when placed close to the airway, whereas the continuous VMN delivered the most when positioned near the ventilator.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"64-70"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794452","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":"Inspiratory Profiles Through Easyhaler Dry Powder Inhaler During Acute Bronchoconstriction.","authors":"Ville A Vartiainen, Antti Tikkakoski, L Pekka Malmberg, Liisa Vuotari, Satu Lähelmä, Ulla Sairanen, Mikko Vahteristo, Jussi Karjalainen, Lauri Lehtimäki","doi":"10.1089/jamp.2024.0045","DOIUrl":"10.1089/jamp.2024.0045","url":null,"abstract":"<p><p><b><i>Background:</i></b> Dry powder inhalers (DPIs) are passive devices, which rely on a patient's inspiratory effort for drug dispersion and delivery. The aim of this study was to assess how acute bronchoconstriction affects the ability to use Easyhaler DPI in adults. <b><i>Methods:</i></b> This study was conducted as part of a parallel-group clinical trial assessing use of Salbutamol Easyhaler, Budesonide-formoterol Easyhaler and salbutamol pMDI with spacer during a methacholine challenge (MC) test. The inhalations through both Easyhaler variants, the inhaler for the single active substance product (EH-mono) and the inhaler for the combination product (EH-combi), were recorded at baseline and during bronchoconstriction. Peak inspiratory flow (PIF), flow rate acceleration and inhalation volume after PIF were compared to the criteria for successful inhalation. <b><i>Results:</i></b> The study population consisted of 120 adult subjects indicated for MC as a diagnostic test for asthma, with 60 subjects in both Easyhaler arms. With EH-combi 98.3% and 91.4% passed the criteria (PIF ≥30 L/min, inhalation acceleration ≥0.7 L/s², and inhalation volume ≥500 mL after PIF) for successful inhalation at baseline and during bronchoconstriction, respectively. With EH-mono, success rates were 95.0% and 88.1% at baseline and during bronchoconstriction, respectively. The most common reason for not passing the criteria was slow inhalation acceleration. Aside from two subjects using EH-mono during bronchoconstriction, all subjects were able to generate PIF ≥ 30 L/min. <b><i>Conclusions:</i></b> During an acute obstructive event, the vast majority of patients have no difficulty in achieving sufficient PIF, inhalation acceleration, and volume after PIF when using an Easyhaler DPI.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"83-89"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364781","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":"Inhaled Chemotherapy.","authors":"Janakiraman Subramanian, Rajiv Dhand","doi":"10.1089/jamp.2025.19211.js","DOIUrl":"10.1089/jamp.2025.19211.js","url":null,"abstract":"<p><p>Cytotoxic chemotherapy remains the cornerstone of treatment for patients diagnosed with advanced stage cancers and is an important component in the multi-disciplinary treatment of several early stage cancers. In the majority of patients with cancer, cytotoxic chemotherapy is administered intravenously and in some instances by oral administration. Systemic administration of cytotoxic chemotherapy is well known to cause adverse effects, which can be severe and debilitating. Regional therapy with cytotoxic agents has the potential to reduce the extent of systemic exposure to the drug and reduce the risk of systemic adverse effects. Regional chemotherapy has been successfully employed in the treatment of certain solid tumors such as hepatocellular carcinoma. However, regional chemotherapy has not been commonly utilized for treatment of lung tumors. Inhaled cytotoxic chemotherapy has the potential to become an effective regional therapy for both primary lung cancer and metastases to the lung from other primary tumors. Aerosol administration of chemotherapy could potentially avoid some of the adverse effects seen with systemic therapy. In addition, some chemotherapeutic agents when administered as an aerosol are absorbed directly into the arterial circulation and have therapeutic effects at extrapulmonary sites. Aerosol administration of several different chemotherapeutic agents is currently under evaluation either in the preclinical setting or in early phase human trials. Some of these studies have shown that inhaled chemotherapy is feasible and effective in treating lung tumors. In this chapter, we review the published studies and ongoing trials on inhaled chemotherapy to better understand the current status of this field of cancer treatment.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"38 2","pages":"90-101"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764082","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":"Comparison of Systemic Exposure Between Epinephrine Delivered via Metered-Dose Inhalation and Intramuscular Injection.","authors":"Jack Yongfeng Zhang, Mary Ziping Luo, Tony Marrs, Edward M Kerwin, Don A Bukstein","doi":"10.1089/jamp.2024.0025","DOIUrl":"10.1089/jamp.2024.0025","url":null,"abstract":"<p><p><b><i>Background:</i></b> Primatene^® MIST, an epinephrine metered-dose inhaler (MDI), has long been questioned by some medical professionals for asthma treatment despite having been approved by the Food and Drug Administration. One of the primary reasons for their concerns stemmed from potential cardiovascular complications following epinephrine administration. However, the majority of documented cardiovascular complications seemed to occur following the injection route of the epinephrine. The aim of this study was to evaluate the systemic exposure of epinephrine delivered through different administration routes and to understand its relationship with cardiovascular effects. Since albuterol inhalers are commonly recommended for asthma, albuterol was also studied as a comparator drug. <b><i>Method:</i></b> A randomized, evaluator-blinded, three-arm crossover study was conducted in 28 healthy adult subjects to compare the profiles of systemic exposure for epinephrine delivered by MDI versus epinephrine intramuscular (IM) injection and albuterol MDI. Serially sampled plasma epinephrine and albuterol levels were measured and compared between treatment groups. Safety was assessed by adverse events, serial vital signs, electrocardiograms (ECGs), and clinical laboratory tests obtained at each crossover dosing visit. <b><i>Results:</i></b> Systemic exogenous drug exposure for inhaled epinephrine MDI (39 pg/mL × hour) was ∼9 times lower than that of epinephrine IM (435 pg/mL × hour) and 122 times lower than that of albuterol MDI (3453 pg/mL × hour) after dose normalization. The C_max in epinephrine MDI (345 pg/mL) was approximately half of that of epinephrine IM (816 pg/mL) and that of albuterol MDI (681 pg/mL). Plasma drug concentrations for epinephrine MDI dropped rapidly to baseline (∼0.6 hour), while epinephrine IM took ∼8 hours, and albuterol MDI required more than 24 hours. Epinephrine MDI and albuterol MDI resulted in minimal, clinically insignificant changes in vital signs and ECGs, whereas epinephrine IM led to mild transient increases in systolic blood pressure, heart rate, and corrected QT interval. <b><i>Conclusion:</i></b> Epinephrine MDI (Primatene MIST) had ∼9 times lower systemic drug exposure (SDE) than that of epinephrine IM and ∼122 times lower than that of albuterol MDI. The lower SDE of inhaled epinephrine also correlated with reassuring safety findings, with no significant cardiovascular adverse effects found, compared with transient effects seen after IM epinephrine. <b>Clinical trial registration number:</b> NCT04207840.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"71-82"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107713","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":"Acknowledgment of Reviewers 2024.","authors":"","doi":"10.1089/jamp.2024.11568.revack","DOIUrl":"https://doi.org/10.1089/jamp.2024.11568.revack","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"38 1","pages":"37"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370638","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":"Pharmaceutical, Clinical, and Regulatory Challenges of Reformulating Pressurized Metered-Dose Inhalers to Reduce Their Environmental Impact.","authors":"Nicolas Roche, Omar Usmani, Laura Franzini, Lorenza Labadini, Kusum S Mathews, Sara Panigone, Job F M van Boven","doi":"10.1089/jamp.2024.0023","DOIUrl":"10.1089/jamp.2024.0023","url":null,"abstract":"<p><p>The chlorofluorocarbons (CFCs) that were used as propellants in early pressurized metered-dose inhalers (pMDIs) had substantial ozone-depleting potential. Following the Montreal Protocol in 1987, the manufacture of a range of ozone-depleting substances, including CFCs, was gradually phased out, which required the propellants used in pMDIs to be replaced. Current pMDIs use hydrofluoroalkanes (HFAs) as propellants, such as 1,1,1,2-tetrafluoroethane (HFA-134a). Although these HFAs have no ozone-depleting potential, they have a high global warming potential (GWP), and consequently, their use is being phased down. One option for the discontinuation of HFA use in inhalers would be to discontinue all pMDIs, switching patients to dry powder inhalers (DPIs). However, a switch from pMDIs to DPIs may not be a clinically appropriate option for some patients; furthermore, the full lifecycle carbon footprint and the overall environmental impact of different inhalers should be considered. An alternative is therefore to reformulate the current HFA pMDIs to use low-GWP propellants, such as 1,1-difluoroethane (HFA-152a). This article summarizes the various steps and challenges associated with this change, illustrated using data from the inhaled triple combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide, a complex formulation of three molecules in a solution that contains liquid-phase propellant.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"26-36"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590626","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}