Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Radiolabeling Methods.","authors":"Myrna B Dolovich","doi":"10.1089/jamp.2022.29067.md","DOIUrl":"https://doi.org/10.1089/jamp.2022.29067.md","url":null,"abstract":"<p><p><i>In vivo</i> measurements of the deposition of an inhaled radiolabeled pharmaceutic have provided useful information related to the inhaler efficiency for depositing drug in the lung. A number of labeling techniques have been developed and applied to pharmaceutical aerosols delivered by pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs) and nebulizers; the choice of radiotracer depends on the type of imaging study being performed and the equipment used to image the lung. Preparation, validation and calibration of the radiolabeled pharmaceutical product is key to successful interpretation of the imaging study. When imaging a subject after inhalation of a radiolabeled formulation, it is the radioactivity that is detected and measured by the scanner; absolute amounts of deposited drug are inferred from the counts of radioactivity in the lung and other regions, based on the assumption that there is a 1:1 relationship between the two components-drug and radioactivity. This relationship holds true for direct-labeled PET products or for those formulations where a firm bond can be demonstrated between the drug and radiotracer for the time taken to acquire all the images. This chapter will discuss radiolabeling methods applied to therapeutic aerosols for the purpose of determining the deposition efficiency of these aerosols in the lung. The techniques apply to both <i>in vivo</i> studies in man and in animal models, and to some extent to <i>in vitro</i> models.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40504670","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":"Adrenaline Inhalation Under Tracheal Intubation by High-Flow Nasal Cannula for Laryngeal Edema.","authors":"Kaname Uchida,&nbsp;Hidehito Ota,&nbsp;Mieko Maezawa,&nbsp;Kenichiro Hayashi,&nbsp;Hikoro Matsui","doi":"10.1089/jamp.2021.0067","DOIUrl":"https://doi.org/10.1089/jamp.2021.0067","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40399606","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":"Empirical Deposition Correlations.","authors":"Andrew R. Martin, W. Finlay","doi":"10.1089/jamp.2022.29062.arm","DOIUrl":"https://doi.org/10.1089/jamp.2022.29062.arm","url":null,"abstract":"Traditionally, empirical correlations for predicting respiratory tract deposition of inhaled aerosols have been developed using limited available in vivo data. More recently, advances in medical image segmentation and additive manufacturing processes have allowed researchers to conduct extensive in vitro deposition experiments in realistic replicas of the upper and central branching airways. This work has led to a collection of empirical equations for predicting regional aerosol deposition, especially in the upper, nasal and oral airways. The present section reviews empirical correlations based on both in vivo and in vitro data, which may be used to predict total and regional deposition. Equations are presented for predicting total respiratory deposition fraction, mouth-throat fraction, nasal, and nose-throat fractions for a large variety of aerosol sizes, subject age groups, and breathing maneuvers. Use of these correlations to estimate total lung deposition is also described.","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75843927","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 a Surfactant Additive on Drug Transport and Distribution Uniformity After Aerosol Delivery to <i>Ex Vivo</i> Lungs.","authors":"Nicholas D Hages,&nbsp;John C Sembrat,&nbsp;Lawrence Weber,&nbsp;Darragh J Johnston,&nbsp;Amy Z Stetten,&nbsp;Madeline Sauleda,&nbsp;Brian Mulhern,&nbsp;Robert D Tilton,&nbsp;Stephen Garoff,&nbsp;Mauricio Rojas,&nbsp;Timothy E Corcoran","doi":"10.1089/jamp.2021.0006","DOIUrl":"https://doi.org/10.1089/jamp.2021.0006","url":null,"abstract":"<p><p><b><i>Background:</i></b> Inhaled drug delivery can be limited by heterogeneous dose distribution. An additive that would disperse drug over the internal surfaces of the lung after aerosol deposition could improve dosing uniformity and increase the treated area. Our previous studies demonstrated that surfactant additives can produce surface tension-driven (Marangoni) flows that effectively dispersed aerosol-delivered drugs over mucus surfaces. Here we sought to determine whether the addition of a surfactant would increase transport of an aerosol between lung regions and also improve dosing uniformity in human lungs. <b><i>Methods:</i></b> We compared the deposition and postdeposition dispersion of surfactant (10 mg/mL dipalmitoylphosphatidylcholine; DPPC) and saline-based liquid aerosols, admixed with Technetium 99m (Tc99m) diethylenetriaminepentaacetic acid, using gamma scintigraphy. Deposition images were obtained <i>ex vivo</i> in eight pairs of ventilated human lungs. The trachea was intubated and the mainstem bronchi were alternately clamped so that saline was delivered to one lung and then DPPC to the other (sides alternated). The lungs were continually imaged for 15 minutes during delivery. We assessed transport of the deposited aerosol by quantifying the percentage of Tc99m in each of four lung quadrants over time. We quantified dose uniformity within each lung quadrant by measuring the coefficient of variation (CV = standard deviation of the pixel associated radioactive counts/mean of the counts within each quadrant). <b><i>Results:</i></b> There was no change in the percentage of Tc99m in each quadrant over time, indicating no improvement in transport with the addition of the surfactant. The addition of surfactant was associated with a statistically significant decrease in CV in the lower inner lung quadrant at each of the three time points, indicating an improvement in dosing uniformity. <b><i>Conclusion:</i></b> These preliminary results indicate the possible utility of adding surfactant to aerosols to improve drug distribution uniformity to lower inner lung regions.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242716/pdf/jamp.2021.0006.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9554769","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":"Optimal Inhalation Flow Pattern from Turbuhaler Predicted by Laser Photometry.","authors":"Tetsuri Kondo,&nbsp;Makoto Hibino,&nbsp;Toshimori Tanigaki,&nbsp;Sakurako Tajiri,&nbsp;Shigeto Horiuchi","doi":"10.1089/jamp.2021.0001","DOIUrl":"https://doi.org/10.1089/jamp.2021.0001","url":null,"abstract":"<p><p><b><i>Background:</i></b> The emitted dose (ED) from most dry powder inhalers (DPIs) is almost independent of peak inspiratory flow (PIF) above a certain value, which is specific to the individual DPI. However, the ED of the Turbuhaler^® (TBH) increases linearly with PIF increments. This study investigated the powder clearance and clinical utility of TBH performance features by using the photo-reflection method (PRM), a type of laser photometry. <b><i>Methods:</i></b> Pulmicort^® (PLM) (containing budesonide only) and Symbicort^® (SMB) (drugs with lactose particles) were inspired with a ramp-up pattern of several PIF intensities using a vacuum pump. Time trajectories of particle release and PIF were then compared. <b><i>Results:</i></b> The particle-release trajectories from both types of DPIs were similar, consisting of a sharp increment phase (∼0.15 seconds) followed by exponential decay. Both onset to the peak of particle-release time and particle-release times were not affected by PIF changes when the PIF was >40 L/min. EDs from both TBHs were linearly related to PIFs, and the slope of the regression equation for SMB was 2.4-fold larger than that of PLM. The peak of the released particles (PK_IED) was also linearly related to PIF. A linear relationship was also observed between ED and PK_IED in both TBHs, and these regression lines overlapped. <b><i>Conclusion:</i></b> EDs from the TBH were dependent on PK_IED. Therefore, rapid, initially strong, and deep inhalation should be advised while using the TBH. PRM could measure the fine and small amount of particles released from the TBH.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39509311","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>In Vitro</i> Performance of the Wixela Inhub Inhaler Using Severe Chronic Obstructive Pulmonary Disease Patient Inhalation Profiles.","authors":"Thomas Shepherd,&nbsp;Matthew Kennett,&nbsp;Andrew Cooper,&nbsp;Adrian Parkinson","doi":"10.1089/jamp.2021.0017","DOIUrl":"https://doi.org/10.1089/jamp.2021.0017","url":null,"abstract":"<p><p><b><i>Background:</i></b> Wixela Inhub (trademarks of Viatris, Inc.) is a dry powder inhaler (DPI) that delivers a fixed-dose combination of fluticasone propionate and salmeterol and is approved as a generic equivalent to Advair Diskus (trademarks of GlaxoSmithKline plc) for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The dosing performance of DPIs is dependent on the patient's inspiratory capability, which may be impacted in disease populations such as those with severe COPD. The objective of this study was to evaluate the <i>in vitro</i> dose delivery of fluticasone propionate and salmeterol from the Inhub inhaler with <i>in vivo</i> inhalation profiles of severe COPD patients, using two types of breathing simulator with different modes of operation. <b><i>Materials and Methods:</i></b> Two breathing simulators (Si-Plan and Copley BRS3100) were used with United States Pharmacopoeia (USP) <601> apparatus 5 (Next Generation Impactor and accessories) to measure the total emitted dose and fine particle mass of fluticasone propionate and salmeterol for Wixela Inhub (250/50 mcg) using 13 severe COPD patient inhalation profiles. <b><i>Results:</i></b> Wixela Inhub demonstrated low flow dependency across the range of COPD patient profiles tested (peak inspiratory flow rate 60.8-84.9 L minute^-1), when assessed by total emitted dose and fine particle mass. The results were similar to literature results reported for fluticasone propionate from the Diskus inhaler, tested using a proprietary breathing simulator and Andersen Cascade Impactor. Comparison between the breathing simulators showed no significant difference in fluticasone propionate results, but a small difference was observed between the breathing simulators for salmeterol total emitted dose and fine particle mass. <b><i>Conclusions:</i></b> This study demonstrates that severe COPD patients are likely to achieve a consistent inhaled dose from Wixela Inhub, with low flow dependency observed within this patient population. In addition, both breathing simulators, which differ significantly in design, produced similar results for fluticasone propionate, but yielded slightly (but statistically significant) different results for salmeterol.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/5e/jamp.2021.0017.PMC9242708.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10470704","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":"Investigating the Accuracy of the Digihaler, a New Electronic Multidose Dry-Powder Inhaler, in Measuring Inhalation Parameters.","authors":"Henry Chrystyn,&nbsp;Dinesh Saralaya,&nbsp;Anil Shenoy,&nbsp;Sophie Toor,&nbsp;Kari Kastango,&nbsp;Enric Calderon,&nbsp;Thomas Li,&nbsp;Guilherme Safioti","doi":"10.1089/jamp.2021.0031","DOIUrl":"https://doi.org/10.1089/jamp.2021.0031","url":null,"abstract":"<p><p><b><i>Background:</i></b> The Digihaler^® is a Food and Drug Administration-approved, digital multidose dry powder inhaler with an integrated electronic module that provides patients and health care professionals with feedback on inhalation parameters, including usage, adherence, and technique. This study compared inhalation parameters measured using the Digihaler with readings made simultaneously using an inhalation profile recorder (IPR). <b><i>Methods:</i></b> This single-visit, open-label study enrolled children (4-17 years) and adults (18-55 years) with asthma, and adults (≥55 years) with chronic obstructive pulmonary disease (COPD). Participants made three separate inhalations using an empty Digihaler device, each measured simultaneously by the Digihaler and IPR. Inhalation profiles were downloaded from the devices at the end of the study. Inhalation parameters measured included peak inspiratory flow (PIF) and inhaled volume (inhV). The profile with the highest PIF and corresponding IPR profile were analyzed. <b><i>Results:</i></b> Overall, 150 participants were enrolled; inhalation data were available for 148 (50 children and 49 adults with asthma, and 49 with COPD). Mean (standard deviation [SD]) age was 39.1 (24.5) years; 51% of participants were male. Overall mean (SD) PIFs as measured by the Digihaler and IPR were 70.62 (17.73) L/min and 72.55 (19.42) L/min, respectively, with a mean percentage difference of -1.75% (95% confidence interval [CI]: -3.64 to 0.15). Mean percentage differences between the Digihaler and IPR measurements of PIF ranged from -2.97% among adults with COPD to 0.16% among children with asthma. Overall mean (SD) inhV for the Digihaler and IPR were 1.57 (0.69) L and 1.67 (0.73) L, respectively, with a mean percentage difference of -6.11 (95% CI: -8.08 to -4.13). There was a strong correlation between PIF and inhV measurements taken by the Digihaler and those taken by the IPR (Spearman's correlation coefficient = 0.96). <b><i>Conclusions:</i></b> Our findings confirm the ability of the Digihaler to provide accurate measurement of inhalation parameters when used by patients.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10528077","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":"Spray Drying and Particle Engineering in Dosage Form Design for Global Vaccines.","authors":"Mellissa Gomez,&nbsp;Reinhard Vehring","doi":"10.1089/jamp.2021.0056","DOIUrl":"https://doi.org/10.1089/jamp.2021.0056","url":null,"abstract":"<p><p>Vaccines are a very important tool in the effort to reduce the global burden of infectious diseases. Modern vaccines can be formulated in several ways to induce specific immunity, including through the use of live bacteria, subunit antigens, and even genetic material. However, vaccines typically need to be transported and stored under controlled refrigerated or frozen conditions to maintain potency. This strict temperature control is incompatible with the available infrastructure in many developing countries. One method of improving the thermostability of a vaccine is through drying of a liquid presentation into a dry dosage form. In addition to enhancing the capability for distribution in resource-poor settings, these dry vaccine forms are more suitable for long-term stockpiling. Spray drying is a drying method that has been successfully used to stabilize many experimental vaccines into a dry form for storage above refrigerated temperatures. Additionally, the use of spray drying allows for the production of engineered particles suitable for respiratory administration. These particles can be further designed for increased out-of-package robustness against high humidity. Furthermore, there are already commercial dry powder delivery devices available that can be used to safely deliver vaccines to the respiratory system. The research in this field demonstrates that the resources to develop highly stable vaccines in flexible dosage forms are available and that these presentations offer many advantages for global vaccination campaigns.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39929006","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":"Moving Forward from \"Fine Particle Fraction: The Good and the Bad\".","authors":"J. Mitchell, W. Doub, J. D. Christopher, C. Gruenloh, R. B. Patel, M. Copley, Steven Tignor, S. Stein, S. Lyapustina, Stephen P Newman","doi":"10.1089/jamp.2022.0017","DOIUrl":"https://doi.org/10.1089/jamp.2022.0017","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89917186","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":"Inhaled Delivery of Anti-Pseudomonal Phages to Tackle Respiratory Infections Caused by Superbugs.","authors":"Hak-Kim Chan,&nbsp;Rachel Yoon Kyung Chang","doi":"10.1089/jamp.2021.0045","DOIUrl":"https://doi.org/10.1089/jamp.2021.0045","url":null,"abstract":"<p><p><b><i>Background:</i></b> Respiratory infections are increasingly difficult to treat due to the emergence of multidrug-resistant bacteria. Rediscovery and implementation of inhaled bacteriophage (phage) therapy as a standalone or supplement to antibiotic therapy is becoming recognized as a promising solution to combating respiratory infections caused by these superbugs. To ensure maximum benefit of the treatment, phages must remain stable during formulation as a liquid or powder and delivery using a nebulizer or dry powder inhaler. <b><i>Methods:</i></b><i>Pseudomonas</i>-targeting PEV phages were used as model phages to assess the feasibility of aerosolizing biologically viable liquid formulations using commercial nebulizers in the presence and absence of inhaled antibiotics. The advantages of powder formulations were exploited by spray drying to produce inhalable powders containing PEV phages with and without the antibiotic ciprofloxacin. <b><i>Results:</i></b> The produced phage PEV20 and PEV20-ciprofloxacin powders remained stable over long-term storage and exhibited significant bacterial killing activities in a mouse lung infection model. <b><i>Conclusion:</i></b> These studies demonstrated that inhaled phage (-antibiotic) therapy has the potential to tackle respiratory infections caused by superbugs.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982117/pdf/jamp.2021.0045.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9225769","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}