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COPD and asthma are two of the most common chronic lung diseases, affecting over 545 million people globally and 34 million in the United States. Annual health care costs related to chronic lung disease are estimated at €380 billion in the European Union, and $24-$50 billion in the United States averaging to $4,000 in out-of-pocket costs per person in the U.S. A full-text literature search was conducted for English publications between January 1, 2005-March 18, 2024. It returned over 5,000 publications that were further narrowed using key search words, resulting in 172 peer-reviewed articles. Using their experience and subject expertise, the authors further narrowed the peer-reviewed articles to 55 that were in their opinion relevant. Also, 38 recently published industry reports and news articles specific to downstream effects of inhaler market changes and the future impact were included. The literature suggests that individuals with chronic lung disease face increased challenges with access to inhaled medication due to rising medication costs, discontinuation of branded medications, introduction of generic medications not covered by insurance, exclusionary preferred drug list tactics that force health care providers into non-medical switching of medication or devices, and ongoing medication shortages. Providers experience ongoing hurdles in prescribing appropriate inhaled medications for individuals with chronic lung disease, including increased time and costs spent on administrative tasks due to inhaler denials, a loss of patient trust, and limits on their ability to prescribe appropriate inhaled medication for individuals with chronic lung disease. [ABSTRACT FROM AUTHOR]

There are many types of inhaler device, each with its own characteristics, benefits and limitations. Inhaler device selection should be individualised. Assessment of the patient's inspiratory flow, dexterity, coordination and preferences can help guide selection of a device that the patient can and will use effectively. For patients who require multiple inhaled drugs, prescribing combination inhalers and avoiding the use of more than one type of inhaler device can reduce errors in inhaler technique and improve adherence. Inhaler technique and adherence should be regularly reviewed. Environmental impact of inhalers can be reduced by optimising symptom control to minimise the need for short-acting beta2 agonists, and choosing inhalers with a low carbon footprint. [ABSTRACT FROM AUTHOR]

Background: The prevalence of asthma indicates the importance of studying oral manifestations of inhalers as one of the indications of asthma. This study compares two methods of using inhalers, Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) in asthmatic patients. Methods: 100 asthmatic patients (50 MDI-treated, 50 DPI-treated) and 50 healthy individuals were selected by convincing sampling. The three sampled groups were gender- and age-matched. We performed a clinical examination, recorded the information, and analyzed the data by SPSS21 software using a t-test and one-way ANOVA for quantitative and Pearson’s chi-square test for qualitative indicators. Results: DMFT index (p-value 0.001), fissured tongue (p-value 0.005), xerostomia (p-value 0.001), and dental erosion (p-value: 0.011) in MDI-treated patients were significantly higher than the other two groups, while the geographic tongue (p-value 0.008) was significantly higher in DPI-treated patients than in the other two groups. It showed that periodontal disease and median rhomboid glossitis had no significant difference between the three groups. Conclusion: Due to the higher incidence of manifestations in MDI, it is expected that physicians give more attention to prescribing inhalers and give them the necessary training to maintain oral and dental hygiene. [ABSTRACT FROM AUTHOR]

The aim of this work is to test whether the use of a transparent capsule affects the residual capsule weight after inhalation as a surrogate of the inhaled delivered dose for patients with non-reversible chronic airway disease. Researchers conducted an observational cross-sectional study with patients using a single-dose dry powder inhaler. The weight of the capsule was measured with a precision microbalance before and after inhalation. Ninety-one patients were included, of whom 63 (69.2%) used a transparent capsule. Inhalation with a transparent capsule achieved a weight decrease of 30.1% vs 8.6% for devices with an opaque capsule (P <0.001). These data reinforce the need to provide patients with mechanisms that verify the correct inhalation technique. [ABSTRACT FROM AUTHOR]

Yongpeng Huang, Hui Tang, Xiangyan Meng, Dongxin Liu, Yanli Liu, Bo Chen, Zhiyun Zou State Key Laboratory of NBC Protection for Civilian, Beijing, People’s Republic of ChinaCorrespondence: Bo Chen; Zhiyun Zou, Email NBC_BoChen@163.com; zouzhiyun65@163.comIntroduction: Nanoparticles have the advantages of improving the solubility of poorly water-soluble drugs, facilitating the drug across biological barriers, and reducing macrophage phagocytosis in pulmonary drug delivery. However, nanoparticles have a small aerodynamic particle size, which makes it difficult to achieve optimal deposition when delivered directly to the lungs. Therefore, delivering nanoparticles to the lungs effectively has become a popular research topic.Methods: Nanoaggregate microparticles were used as a pulmonary drug delivery strategy for the improvement of the bioavailability of cyclosporine A (CsA). The nanoaggregate microparticles were prepared with polyvinyl pyrrolidone (PVP) as the excipient by combining the anti-solvent method and spray drying process. The physicochemical properties, aerodynamic properties, in vivo pharmacokinetics and inhalation toxicity of nanoaggregate microparticles were systematically evaluated.Results: The optimal nanoparticles exhibited mainly spherical shapes with the particle size and zeta potential of 180.52 nm and − 19.8 mV. The nanoaggregate microparticles exhibited irregular shapes with the particle sizes of less than 1.6 μm and drug loading (DL) values higher than 70%. Formulation NM-2 as the optimal nanoaggregate microparticles was suitable for pulmonary drug delivery and probably deposited in the bronchiole and alveolar region, with FPF and MMAD values of 89.62% and 1.74 μm. In addition, inhaled NM-2 had Cmax and AUC0-∞ values approximately 1.7-fold and 1.8-fold higher than oral cyclosporine soft capsules (Neoral®). The inhalation toxicity study suggested that pulmonary delivery of NM-2 did not result in lung function damage, inflammatory responses, or tissue lesions.Conclusion: The novel nanoaggregate microparticles for pulmonary drug delivery could effectively enhance the relative bioavailability of CsA and had great potential for clinical application. Keywords: pulmonary drug delivery, dry powder inhalers, nanoaggregate microparticles, aerosol performance, pharmacodynamic study, inhalation toxicity

Improper inhalation technique (IT) is associated with uncontrolled asthma. Continuous training improves IT. The objective was to evaluate IT of patients who had incorrectly demonstrated IT in a previous study (E1), carrying out a new cross-sectional study (E2) with patients who had incorrect IT in E1, carried out 30 months earlier, in the same place, where IT is oriented in every medical appointment. Questionnaire filled out with sociodemographic data, assessment of control using the Asthma Control Test, type of inhalation device (ID) in use, time of use and existence of medical instructions for use. IT was considered correct when all stages of use were carried out properly, according to the medication leaflets. 31 (72.1%) patients from E1 were included. Seventeen (54.8%) used dry powder inhalers (DPI) and 14 (45.2%) metered dose inhlaers (MDI). Fifteen (48.4%) had controlled asthma. All received guidance on how to use their IDs and 21 (67.7%) had been using them for at least 2 years. Twenty-one (67.7%) presented the IT incorrectly. Eight of 17 (47.1%) DPI users and 2 (14.3%) MDI users had the correct IT (p=0.049). IT training gradually improves its quality, but this process is slow. About two-thirds of the sample remained with the wrong IT, especially among AD users. [ABSTRACT FROM AUTHOR]

Optimal peak inspiratory flow rate (PIFR) is required for effective drug delivery to distal airways when using dry powder inhalers (DPIs). This study aimed to examine the association between PIFR and hand grip strength (HGS) in stable COPD patients. A cross-sectional study was conducted. PIFR was measured using the In-check DIAL to assess for Accuhaler and Turbuhaler DPIs. HGS was measured using a handheld dynamometer. A PIFR of

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This section aims to provide a concise and contemporary technical perspective and reference resource covering dry powder inhaler (DPI) formulations. While DPI products are currently the leading inhaled products in terms of sales value, a number of confounding perspectives are presented to illustrate why they are considered surprisingly, and often frustratingly, poorly understood on a fundamental scientific level, and most challenging to design from first principles. At the core of this issue is the immense complexity of fine cohesive powder systems. This review emphasizes that the difficulty of successful DPI product development should not be underestimated and is best achieved with a well-coordinated team who respect the challenges and who work in parallel on device and formulation and with an appreciation of the handling environment faced by the patient. The general different DPI formulation types, which have evolved to address the challenges of aerosolizing fine cohesive drug-containing particles to create consistent and effective DPI products, are described. This section reviews the range of particle engineering processes that may produce micron-sized drug-containing particles and their subsequent assembly as either carrier-based or carrier-free compositions. The creation of such formulations is then discussed in the context of the material, bulk, interfacial and ultimately drug-delivery properties that are considered to affect formulation performance. A brief conclusion then considers the future DPI product choices, notably the issue of technology versus affordability in the evolving inhaler market. [ABSTRACT FROM AUTHOR]

Background Administration of drugs by inhalation is a common route for the treatment of chronic airway diseases. The ability of patients to use an inhaler device is a key factor in the effectiveness of treatment. Recently, a new type of quantitative assessment instrument for inhalation drugs has been developed in China, which can measure peak inspiratory flow (PIF) and inspiratory volume (VI) under conditions with various internal resistance of inhalers, thereby accurately assessing the ability of patients to use inhaler. However, there are no quality testing methods and adoption standards for this type of instrument at home and abroad. Objective To perform quality testing of the inhalation drug quantitative assessment instrument and evaluate its technical performance, in order to explore the application value of the method. Methods Various internal resistance of dry powder inhalers (DPI) was simulated by the inhalation drug quantitative assessment instrument (PF810) in 5 different gears (R1-R5 from low to high) . A standard flow/volume simulator was used to test the flow, volume and impedance performance of the PF810 for inhalation. The flow test was performed at a fixed volume (3.000 L) and different flow rates (in the range of 0-2.000 L/s, with 0.250 L/s as the interval stepwise) . The volume was carried out at three flow rates of low (0.500 L/s) , medium (1.000 L/s) and high (1.500 L/s) , and at different volumes (1.000 L as the interval stepwise in the range of 1.000-4.000 L) . The Bland-Altman analysis chart method of GraphPad prism 9.0 software was used to evaluate the consistency of PIF and VI measurements of the inhalation drug quantitative assessment instrument with the actual values output by the simulator at different resistance gears. Results The results of quality control evaluation of flow detection showed that the percentages of repeatability, accuracy and linearity of flow detection meeting the performance requirements were 100.00% (40/40) , 95.00% (38/40) and 94.29% (33/35) . The accuracy and linearity of PF810 at R5 gear 1.500L /s and above did not meet the performance testing requirements, while those of other gears and flow rates met the requirements. The Bland-Altman consistency test showed 95% limit of agreement (LOA) of (-0.271- 0.107) L/s, with 96.00% (192/200) data points within the 95%LOA range. The results of volume test quality control evaluation showed that the pass rates of volume test repeatability, accuracy and linearity were all 100.00% (60/60, 60/60, 45/45) . The Bland-Altman consistency test showed that 95%LOA was (-0.058-0.017) L, and 100.00% (180/180) data points were within the 95%LOA range. The impedance measurement quality control evaluation results showed that the relative errors between the impedance value of PF810 and the internal resistance of the corresponding inhaler were all

OBJECTIVE: This study aimed to evaluate the impact of a pharmacist-led intervention on improving adherence and practice of inhaler use in outpatients with asthma at a hospital in Vietnam. METHODS: A pre-post interventional study was conducted at Hue University Hospital. An adapted checklist for both metered-dose inhalers and/or dry powder inhalers was used to evaluate the inhaler technique. Adherence was assessed by using the Test of Adherence to Inhalers questionnaire. The means of interventions comprised "Face-to-face training," "Creating the leaflet for patients," and "Watching guidance video.". RESULTS: The number of participants with complete data was 79. Before the intervention, 54.4% of patients had misused inhalers, especially inappropriate posture when using devices (70.2%) and not exhaling before inhalation (46.8%). Non-adherence accounted for 55.7% of patients, and the erratic pattern was the highest, with 83.5%. The intervention had remarkably raised the number of good practice and good adherence patients after three months (P < 0.001). CONCLUSION: Pharmacist-led intervention has a positive impact on improving the adherence to inhalers and inhalation techniques of patients with asthma. PRACTICE IMPLICATIONS: The pharmacist-led education model could be considered as an effective and feasible solution for asthma management in outpatients and better medication use. [ABSTRACT FROM AUTHOR]

In this review, an extensive analysis of dry powder inhalers (DPIs) is offered, focusing on their characteristics, formulation, stability, and manufacturing. The advantages of pulmonary delivery were investigated, as well as the significance of the particle size in drug deposition. The preparation of DPI formulations was also comprehensively explored, including physico-chemical characterization of powders, powder processing techniques, and formulation considerations. In addition to manufacturing procedures, testing methods were also discussed, providing insights into the development and evaluation of DPI formulations. This review also explores the design basics and critical attributes specific to DPIs, highlighting the significance of their optimization to achieve an effective inhalation therapy. Additionally, the morphology and stability of 3 DPI capsules (Spiriva, Braltus, and Onbrez) were investigated, offering valuable insights into the properties of these formulations. Altogether, these findings contribute to a deeper understanding of DPIs and their development, performance, and optimization of inhalation dosage forms. [ABSTRACT FROM AUTHOR]

Dry powder inhalers (DPIs) have gained increasing clinical acceptance in the local treatment of lung diseases due to their ability to meet the evolving needs of patients while avoiding environmental concerns. However, some formulations for DPIs still encounter performance limitations in terms of aerodynamic properties and achievement of therapeutic doses. Innovative aerogel powder formulations for DPIs processed using combined supercritical CO2 (scCO2)-based technologies can overcome these limitations, especially in the case of poorly water-soluble drugs. The loading of hydrophobic drugs into aerogels can be optimized through a thorough understanding of the physicochemical properties of the formulation and the scCO2 processing conditions. In this study, drug-loaded alginate aerogel particles were prepared by combining gelation-emulsification techniques and scCO2-based technologies. Beclomethasone dipropionate (BDP), a hydrophobic corticosteroid, was incorporated into the aerogel matrix by scCO2 impregnation. The influence of contact time, initial amount of drug, and use of co-solvents on the efficiency of scCO2 impregnation were studied. The kinetics of the BDP adsorption process was modelled to elucidate the time required for the drug to attain equilibrium concentration under specific operating conditions. Nitrogen adsorption-desorption and helium pycnometry revealed particles with large surface area (>200 m2/g) and porosity (ca. 90%). The resulting aerogels had excellent aerodynamic properties at relevant BDP doses, as confirmed by in vitro lung deposition tests. Ex vivo permeability tests with porcine lung tissues evidenced that BDP released from the inhaled formulation could penetrate the bronchial tissue.

المخلص: أهداف البحث: العلاج بالاستنشاق هو العلاج المفضل لأمراض الرئة الانسدادي مثل الربو ومرض الانسداد الرئوي المزمن. ومع ذلك، فإن أقصى فائدة من العلاج تعتمد على الاستخدام الصحيح لأجهزة الاستنشاق. في هذه الدراسة، كان هدفنا الأساسي هو تقييم تقنيات استخدام أجهزة الاستنشاق لدى مرضى الربو ومرض الانسداد الرئوي المزمن من أجل تحديد الأخطاء. أيضا، قمنا بفحص تأثير المعلمات المحتملة على معدل إساءة الاستخدام. طرق البحث: تم تسجيل ما مجموعه 300 من مرضى الربو / مرض الانسداد الرئوي المزمن، الذين قدموا عيادات أمراض الصدر وطب الأسرة للمرضى الخارجيين في مستشفى ثالث يقع في أنقرة - تركيا ، في الدراسة. استخدمنا استطلاعًا وجهاً لوجه تضمن أسئلة حول الميزات الاجتماعية والديموغرافية والعلاج بالاستنشاق. بعد ذلك، طلبنا من المرضى توضيح كيفية استخدامهم لأجهزة الاستنشاق وتقييم تقنية الاستنشاق الخاصة بهم بسبب قوائم المراجعة. النتائج: من بين جميع المرضى، كان 70.2٪ يستخدمون أدوية الاستنشاق بشكل غير صحيح. كان معدل إساءة الاستخدام بين مستخدمي أجهزة الاستنشاق بالجرعات المقننة أعلى مقارنة بمستخدمي أجهزة الاستنشاق بالمسحوق الجاف (77.6٪ مقابل 64٪). عند مقارنة أجهزة الاستنشاق بالمسحوق الجاف فيما بينها، كانت معدلات إساءة الاستخدام أعلى بشكل ملحوظ في مستخدمي هانديهالر ومستخدمي أجهزة الاستنشاق ديسكس مقارنة بمستخدمي سانوهالر. تم العثور على الجنس ونوع المرض (الربو / مرض الانسداد الرئوي المزمن) ومدة استخدام جهاز الاستنشاق ومدة المرض ليس لها أي تأثير على سوء الاستخدام. ومع ذلك، فإن العمر المتقدم (> 60 سنة)، ومستوى التعليم الأدنى من المدرسة الثانوية، واستخدام أجهزة الاستنشاق بالجرعات المقننة كانت من العوامل المرتبطة بسوء الاستخدام. كان الخطأ الأكثر شيوعا هو ''عدم التنفس قبل الاستنشاق'' لجميع أنواع الأجهزة (بالنسبة إلى أجهزة الاستنشاق بالجرعات المقننة: 66.7٪ ، و أجهزة الاستنشاق بالمسحوق الجاف: 71.1-82.8٪). الاستنتاجات: تم العثور على معدل إساءة استخدام العقاقير المستنشقة لتكون عالية. من شأن تحديد العوامل المرتبطة بسوء الاستخدام أن يوفر عناصر لتنفيذ الإجراءات لتقليل معدلات فشل العلاج. Abstract: Objectives: Inhaled therapy is the treatment of choice for obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). However, the maximum benefit from such therapy depends on the correct use of inhaler devices. In this study, our primary aim was to evaluate inhaler techniques in patients with asthma and COPD in order to identify common errors. In addition, we investigated the effect of various parameters on the rate of inhaler misuse. Methods: We enrolled a total of 300 asthma/COPD patients, who presented at the Chest Diseases and Family Medicine Outpatient Clinics of a tertiary hospital located in Ankara, Turkey. We used a face-to-face survey that included questions about sociodemographic features and inhaler therapy. Subsequently, we requested patients to demonstrate how they use their inhalers and assessed their inhalation technique according to checklists. Results: Of the 300 patients, 70.2% used their inhaler drugs incorrectly. The rate of misuse among metered dose inhaler (MDI) users was significantly higher than those using dry powder inhalers (DPIs) (77.6% vs 64%; p = 0.002). When DPI devices were analyzed, the rates of misuse were significantly higher in Handihaler users (p = 0.012) and Diskus inhaler users (p = 0.009) when compared to Sanohaler users. Gender, type of disease (asthma/COPD), duration of inhaler use, and duration of illness had no impact on the rate of misuse. However, an advanced age (>60 years old), a level of education lower than high school, and the use of MDI were all identified as factors associated with misuse. The most common mistake was ‘failing to breath out before inhalation’ for all types of devices (for MDI: 66.7%, and for DPI: 71.1–82.8%). Conclusions: The rate of inhaler drug misuse was high. The identification of factors associated with misuse could provide information to implement appropriate actions to reduce the rates of misuse.

The amount of drug depositing in the airways depends, among others, on the inhalation manoeuvre and breathing parameters. The objective of this study was to quantify the effect of lung emptying before the inhalation of drugs on the lung doses. Thirty healthy adults were recruited. Their breathing profiles were recorded while inhaling through six different emptied DPI devices without breathe-out and after comfortable or forced exhalation. The corresponding emitted doses and aerosol size distributions were derived from the literature. The Stochastic Lung Model was used to estimate the deposited doses. In general, forceful exhalation caused increased flow rate and inhaled air volume. Increased flow rate led to the increase of the average lung dose for drugs with positive lung dose-flow rate correlation (e.g. Symbicort®: relative increase of 6.7%, Bufomix®: relative increase of 9.2%). For drugs with negative correlation of lung dose with flow rate (all the studied drugs except the above two) lung emptying caused increased (Foster® by 2.7%), almost unchanged (Seebri®, Relvar®, Bretaris®) and also decreased (Onbrez® by 6.6%) average lung dose. It is worth noting that there were significant inter-individual differences, and lung dose of each drug could be increased by a number of subjects. In conclusion, the change of lung dose depends on the degree of lung emptying, but it is also inhaler and drug specific. Forceful exhalation can help in increasing the lung dose only if the above specificities are taken into account.

Airway deposition of aerosol drugs is highly dependent on the breathing manoeuvre of the patients. Though incorrect exhalation before the inhalation of the drug is one of the most common mistakes, its effect on the rest of the manoeuvre and on the airway deposition distribution of aerosol drugs is not explored in the open literature. The aim of the present work was to conduct inhalation experiments using six dry powder inhalers in order to quantify the effect of the degree of lung emptying on the inhalation time, inhaled volume and peak inhalation flow. Another goal of the research was to determine the effect of the exhalation on the aerodynamic properties of the drugs emitted by the same inhalers. According to the measurements, deep exhalation before drug inhalation increased the volume of the inhaled air and the average and maximum values of the inhalation flow rate, but the extent of the increase was patient and inhaler specific. For different inhalers, the mean value of the relative increase in peak inhalation flow due to forceful exhalation was between 15.3 and 38.4% (min: Easyhaler®, max: Breezhaler®), compared to the case of normal (tidal) exhalation before the drug inhalation. The relative increase in the inhaled volume was between 36.4 and 57.1% (min: NEXThaler®, max: Turbuhaler®). By the same token, forceful exhalation resulted in higher emitted doses and smaller emitted particles, depending on the individual breathing ability of the patient, the inhalation device and the drug metered in it. The relative increase in the emitted dose varied between 0.2 and 8.0% (min: Foster® NEXThaler®, max: Bufomix® Easyhaler®), while the relative enhancement of fine particle dose ranged between 1.9 and 30.8% (min: Foster® NEXThaler®, max: Symbicort® Turbuhaler®), depending on the inhaler. All these effects and parameter values point toward higher airway doses due to forceful exhalation before the inhalation of the drug. At the same time, the present findings highlight the necessity of proper patient education on the importance of lung emptying, but also the importance of patient-specific inhaler-drug pair choice in the future.

In this study, the extra-fine dry powder inhalers (DPIs) with chitosan (CS) as carrier were successfully prepared by ionic gel method combined with spray drying technique for deep pulmonary drug delivery of Cyclosporine A (CsA), using sodium hyaluronate (SHA) and sodium polyglutamate (SPGA) as polyanions. The CsA-loaded DPIs of CS-SHA-CsA and CS-SPGA-CsA were spherical particles with wrinkles on the surface, which were more conducive to improving the aerosol properties. The aerodynamic evaluation of CS-SHA-CsA and CS-SPGA-CsA showed that the fine particle fraction (FPF) reached up to 79.22 ± 2.12% and 81.55 ± 0.43%, while the emitted fraction (EF) reached 77.15 ± 1.46% and 78.29 ± 2.10%. In addition, the mass median aerodynamic diameter (MMAD) was calculated as 1.58 ± 0.04 μm and 1.94 ± 0.02 μm for CS-SHA-CsA and CS-SPGA-CsA, indicating that they were all extra-fine particles (d < 2 μm). These in vitro aerodynamic results showed that CS-SHA-CsA and CS-SPGA-CsA could reach the smaller airways, further improving therapeutic efficiency. The cell viability on A549 cell line results showed that CS-SHA-CsA and CS-SPGA-CsA were safe to deliver CsA to lungs. The in vivo pharmacokinetics consequence proved that inhalation administration of CS-SHA-CsA and CS-SPGA-CsA could significantly improve the bioavailability of CsA in vivo compared with oral administration of Neoral®, effectively reducing the risk of a series of adverse effects caused by systemic overexposure. In addition, the safety and compatibility of DPIs using SHA, SPGA, and CS as carriers for pulmonary drug delivery was verified by in vivo repeated dose inhalation toxicity. From these findings, the extra-fine DPIs with CS as carrier could be a viable delivery option for the deep pulmonary drug delivery of CsA relative to orally administered drug. [Display omitted] • CS nanoparticles were successfully prepared in a short reaction time. • CsA loaded CS DPIs had fine aerosol characteristics and could be delivered into the deep lungs. • Inhalable DPIs could significantly improve the bioavailability of CsA in vivo compared with oral administration of Neoral®. • Repeated dose inhalation toxicity assessment in vivo proved the safety and tolerability of DPIs in the lungs. [ABSTRACT FROM AUTHOR]

Aim. Investigate inhalation techniques using different inhalers types and their effect on the course of disease. Materials and methods. This cross-sectional study included 110 patients with asthma, chronic obstructive pulmonary disease using the inhaler at least one month. Inhaler errors performed during demonstration were evaluated for each patient and entered in the check-lists. We also collected information about co-morbidities, education, mMRC dyspnea score, rate of exacerbations, and performed spirometry. Results. 80.9% of patients used metered-dose inhaler, 20.9% single-dose and 21.8% multiple-dose dry powder inhaler, 22.7% soft-mist inhaler. Inhaler errors were made by 80.9% patients. The mean number of mistakes in metered-dose inhaler use was 21.6, single-dose powder inhaler 1.51.3, multiple-dose dry powder inhaler 1.251.4, soft-mist inhaler 0.680.7 (р=0.003). Age, diagnosis, duration of disease, education level, inhalers usage by relatives have no influence on the inhalation technique. A number of errors was related to female gender (р=0.007) and usage of more than 2 inhalers (r=0.3, p=0.002), previous instruction about inhalation technique (r=0.3, p=0.001). On the other hand, there were correlations between the number of errors and degree of bronchial obstruction, asthma control, severity of dyspnea by mMRC score, exacerbation rate. Conclusion. Patients with bronchoobstructive diseases perform many inhaler errors, that substantially influences the severity and course of asthma and chronic obstructive pulmonary disease.

Breath-actuated inhalers (BAIs) are gaining attention in the management of obstructive airway diseases (OADs). In Nepal, a BAI containing fluticasone propionate/salmeterol (FPS) has been available for a year. This survey is aimed at determining the perception and experience of physicians in Nepal concerning BAIs. A cross-sectional, questionnaire-based survey was conducted. A total of 141 physicians participated and filled the survey. Most physicians felt that the right device should be easy to teach, learn and remember. They considered coordination and multiple steps as the primary challenges with pressurized metered-dose inhalers and dry powder inhalers, respectively. Most of them agreed that BAIs could address these challenges. BAIs were not only preferred by most of the physicians for asthma and chronic obstructive pulmonary disease but were also the preferred choice in newly diagnosed patients. Physicians believed that if current patients were shifted to BAIs, it could improve inhalation technique (88%) and compliance/adherence (81%). Almost all of them (92–97%) agreed that teaching the breathing technique and the cleaning process was easier and faster in BAIs. BAIs were considered easy and simple to use. Also, BAI's dose-counter helps patients to increase adherence to inhalation therapy. In this INTROSPECT survey, physicians in Nepal believed that BAIs could address the key challenges faced with using pMDIs and DPIs in asthma and COPD patients. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from Stephania cepharantha Hayata. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (Da) of the DPIs was 3.2 μm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model's establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (p < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI. [ABSTRACT FROM AUTHOR]

Objective The core treatment for asthma and chronic obstructive pulmonary disease (COPD) is inhalers. Today, there are many types of pressurized metered-dose inhalers (pMDIs) and dry powdered inhalers (DPIs). Each inhaler requires special sequential manoeuvres and coordination. It is well-known from previous studies that most patients perform at least one mistake using their inhaler which may lead to ineffective drug delivery and poor disease control. The aim of this study is to measure the proportion of patients who used the inhalers in a fully effective way before and after the pharmacist's guidance. Methods Patients prescribed inhalers for asthma and COPD, were offered by the local pharmacist to personally assess and correct their inhaler use technique over two visits. At each visit, before any pharmacist correction of technique, a general score for inhaler technique was given and 16 types of mistakes were assessed. Comparisons of inhaler technique were made between the two visits. Key findings Sixty patients aged 21–91 (median 69; IQR 48–78) participated in the initial session of which 35 (58%) were females using 81 inhalers (DPI-60, pMDI-21). A fully effective inhaler technique was found in nine patients (15%) using 13 inhalers (16%) while 22 inhalers (27%) were used fully ineffectively (there were no statistically significant differences between DPIs and pMDIs). Twenty-three patients using 24 inhalers returned for a second visit in which 12 patients (52%, P = 0.0014 between the visits) used 12 inhalers (50%) fully effectively and only three inhalers (12.5%) were used fully ineffectively (P = 0.0045 between the visits). The odds for using the inhaler fully effectively were 5.2 (95% CI, 1.9 to 14.2; P = 0.0011) times higher on the second visit. Conclusions Personal pharmacist guidance can improve inhaler technique in a low socio-economic neighbourhood. However, larger multicentre studies that will also examine clinical outcomes are needed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the in vitro lung dissolution of amorphous and crystalline powder formulations of rifampicin in polyethylene oxide (PEO) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), and to predict the in vivo plasma concentration–time profiles using the in vitro data. Methods: The in vitro dissolution and permeation profiles of respirable rifampicin particles were studied using a custom-made dissolution apparatus. Data from the in vitro dissolution test were used to estimate the parameters to be used as the input for the simulation of in vivo plasma concentration–time profiles using STELLA® software. For prediction of in vivo profiles, a one-compartment model either with a first order elimination or with a Michaelis–Menten kinetics-based elimination was used. Results: Compared to the crystalline formulation, the amorphous formulation showed rapid in vitro dissolution suggesting their possible faster in vivo absorption and higher plasma concentrations of rifampicin following lung delivery. However, the simulations suggested that both powder formulations would result in similar plasma-concentration time profiles of rifampicin. Conclusions: Use of an in vitro dissolution test coupled with a simulation model for prediction of plasma-concentration time profiles of an inhaled drug was demonstrated in this work. These models can also be used in the design of inhaled formulations by controlling their release and dissolution properties to achieve desired lung retention or systemic absorption following delivery to the lungs. [ABSTRACT FROM AUTHOR]

For patients with lung disease, dry powder inhalers (DPI) are profoundly beneficial. The current study introduces and develops a series of dry powder inhalers (DPIs). A capsule-based (size 0) active DPI was considered. The study aims to investigate whether swirling flow and outlet capillary diameter (dc_out) affect the percentage of emitted doses (ED) released from the capsule. Spiral vanes were added to the capillary inlet to produce a swirling flow. Computational fluid dynamics (CFD) was applied to simulate the problem. The results were compared with previous in vitro and numerical studies to validate the results. Based on the derived results, the small swirl parameter (SP) enhances the secondary flow and recirculation zone. It increases the central jet flow, which increases the ED value by about 5–20% compared to no-swirl flow. However, as the airflow rate increases, the recirculation zone enlarges, vorticities become dominant, and asymmetrical flow patterns emerge. Consequently, ED % drops significantly (more than 50%). As dc_out decreases, the vorticities around the outlet capillary become more potent, which is undesirable. Indeed, the emptying of the capsule does not happen ideally. The research provides a perspective on the device's design and DPI performance.

Trehalose is commonly used as a protein stabilizer in spray dried protein formulations delivered via the pulmonary route. Spray dried trehalose formulations are highly hygroscopic, which makes them prone to deliquescence and recrystallization when exposed to moisture, leading to impairment in aerosolization performance. The main aim of this study was to investigate and compare the effect of hydrophobic amino acids (i.e. L-leucine and L-isoleucine) in enhancing aerosolization performance and in mitigating moisture-induced changes in spray dried trehalose formulations. Trehalose was spray dried with 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine). The spray dried formulations were stored at 25 °C/50% RH for 28 days. Solid state characterization and in vitro aerosolization performance studies were performed on the spray dried formulations before and after storage. The addition of 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine) improved the emitted fractions of spray dried trehalose formulations from a dry powder inhaler. However, ≥ 40% w/w of L-leucine/L-isoleucine was needed to prevent recrystallization of trehalose in the formulations when exposed to 25 °C/50% RH for 28 days. X-ray photoelectron spectroscopy (XPS) demonstrated that samples with 40-60% w/w L-isoleucine had more amino acid on the surfaces of the particles compared to their L-leucine counterparts. This may explain the greater ability of the L-isoleucine (40-60% w/w) samples to cope with elevated humidity compared to L-leucine samples of the same concentrations, as observed in the dynamic vapour sorption (DVS) studies. In conclusion, this study demonstrated that both L-leucine and L-isoleucine were effective in enhancing aerosolization performance and mitigating moisture-induced reduction in aerosolization performance in spray dried trehalose formulations. L-isoleucine proved to be superior to L-leucine in terms of its moisture protectant effect when incorporated at the same concentration in the formulations.

The use of inhaled, fixed-dose, long-acting muscarinic antagonists (LAMA) combined with long-acting, beta2-adrenergic receptor agonists (LABA) has become a mainstay in the maintenance treatment of chronic obstructive pulmonary disease (COPD). One of the fixed-dose LAMA/LABA combinations is the dry powder inhaler (DPI) of umeclidinium bromide (UMEC) and vilanterol trifenatate (VI) (62.5 µg/25 µg) approved for once-a-day maintenance treatment of COPD. This paper reviews the use of fixed-dose combination LAMA/LABA agents focusing on the UMEC/VI DPI inhaler in the maintenance treatment of COPD. The fixed-dose combination LAMA/LABA inhaler offers a step beyond a single inhaled maintenance agent but is still a single device for the COPD patient having frequent COPD exacerbations and persistent symptoms not well controlled on one agent. Currently available clinical trials suggest that the once-a-day DPI of UMEC/VI is well-tolerated, safe and non-inferior or better than other currently available inhaled fixed-dose LAMA/LABA combinations for COPD.

Carrier-free spray-dried dispersions for pulmonary delivery, for which the demand is growing, frequently require the incorporation of dispersibility-enhancing excipients into the formulations to improve the efficacy of the dosage form. One of the most promising of such excipients, L-leucine, is expected to be approved for inhalation soon and has been studied exhaustively. However, during stability, small fibers protruding from the particles of leucine-containing powders have occasionally been observed. To clarify the origin of these fibers and assess their potential influence on the performance of the powders, three different classes of spray-dried leucine-containing formulation systems were studied over an 8-month accelerated stability program. These systems consisted of a large molecule biologic (bevacizumab) in conjunction with a glass former (trehalose), an amorphous small-molecular mass active (moxidectin), and a crystallizing active (mannitol). It was determined that the appearance of the fibers was due to the presence of small quantities of leucine in higher energy states, either because these were amorphous or present as a less stable crystalline polymorph. It was further shown that the growth of these leucine fibers caused no significant physicochemical instability in the powders. Nor, more importantly, did it decrease their aerosol performance in a dry powder inhaler or reduce the concentration of their active pharmaceutical ingredients. [ABSTRACT FROM AUTHOR]

Purpose: The probability of agglomerate-to-wall collision was quantified using a unique image processing technique applied to high-speed microscopic images. The study aimed to investigate the effects of flow rate and particle size on the percentage of colliding agglomerates detected within an in-house powder dispersion device. Method: The device consists of a swirl chamber and two tangential inlets in various configurations, designed to emulate the geometric features of commercial devices such as the Aerolizer® and Osmohaler®. The test cases were conducted with constant flow rates of 30 SLPM and 60 SLPM. Four powder samples were tested, including carrier Respitose® SV010 (median volume diameter 104 µm, span 1.7) and mannitol of three constituent primary particle sizes (3 µm, 5 µm and 7 µm; span 1.6 – 1.9). Results: At the lower flow rate of 30 SLPM, collision frequencies were significantly different between powders of different constituent particle sizes, but the effects of powder properties diminished on increasing the flow rate to 60 SLPM. At the higher flow rate, all powders experienced a significant increase in the proportion of colliding particles. Conclusion: Analysis of collision events showed that the probability of collision for each agglomerate increased with agglomerate diameter and velocity. Experimental data of agglomerate-to-wall collision were utilised to develop a logistic regression model that can accurately predict collisions with various powders and flow rates. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has proven to be an unprecedented health crisis in the human history with more than 5 million deaths worldwide caused to the SARS-CoV-2 and its variants (https://www.who.int/emergencies/diseases/novel-coronavirus-2019). The currently authorized lipid nanoparticle (LNP)–encapsulated mRNA vaccines have been shown to have more than 90% vaccine efficacy at preventing COVID-19 illness (Baden et al. New England J Med 384(5):403–416, 2021; Thomas et al., 2021). In addition to vaccines, other small molecules belonging to the class of anti-viral and anti-inflammatory compounds have also been prescribed to reduce the viral proliferation and the associated cytokine storm. These anti-viral and anti-inflammatory compounds have also been shown to be effective in reducing COVID-19 exacerbations especially in reducing the host inflammatory response to SARS-CoV-2. However, all of the currently FDA-authorized vaccines for COVID-19 are meant for intramuscular injection directly into the systemic circulation. Also, most of the small molecules investigated for their anti-COVID-19 efficacy have also been explored using the intravenous route with a few of them explored for the inhalation route (Ramakrishnan et al. Lancet Respir Med 9:763–772, 2021; Horby et al. N Engl J Med 384(8):693–704, 2021). The fact that the SARS-CoV-2 enters the human body mainly via the nasal and airway route resulting in the lungs being the primary organs of infection as characterized by acute respiratory distress syndrome (ARDS)–mediated cytokine storm in the alveolar region has made the inhalation route gain significant attention for the purposes of targeting both vaccines and small molecules to the lungs (Mitchell et al., J Aerosol Med Pulm Drug Deliv 33(4):235–8, 2020). While there have been many studies reporting the safety and efficacy of targeting various therapeutics to the lungs to treat COVID-19, there is still a need to match the choice of inhalation formulation and the delivery device platform itself with the patient-related factors like breathing pattern and respiratory rate as seen in a clinical setting. In that perspective, this review aims to describe the various formulation and patient-related clinical factors that can play an important role in the judicious choice of the inhalation delivery platforms or devices for the development of inhaled COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Copyright of Revista Salud UIS is the property of Universidad Industrial de Santander and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases. Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution, leading to a more effective therapy with reduced required doses and side effects. On the other hand, there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical, aerodynamic and biological properties, which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result. Therefore, we focused on powders consisting of polysaccharides, lipids, proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers. We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms. This review article addresses the most common manufacturing methods with novel modifications, pros and cons of different materials, drug loading capacities with release profiles, and biological properties such as cytocompatibility, bactericidal or anticancer properties. [ABSTRACT FROM AUTHOR]

Background: Greater patient satisfaction with his or her inhalation device is associated with better adherence to pharmacological therapy and better clinical outcomes, such as improved quality of life, greater asthma control, and fewer exacerbations. The objective of this study was to determine the satisfaction level of a group of patients diagnosed with bronchial asthma concerning their devices for inhalation of bronchodilators and glucocorticoids. Methods: This was a cross-sectional study of patients treated in the Colombian health system. Satisfaction with inhalation devices was evaluated with the Feeling of Satisfaction with Inhaler (FSI)-10 questionnaire. A score of ≥44 points indicated high satisfaction. Results: In total, 362 patients from 59 cities were identified, their median age was 55 years, and 74.6% were women. The FSI-10 average score was 44.6; 68.5% of patients showed high satisfaction, especially with pressurized metered-dose inhalers (pMDIs), and 63.4% did not use them with an inhalation chamber. Users of pMDIs (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.05–3.10) and those who received training by medical specialists (OR: 2.29; 95% CI: 1.33–3.97) had high satisfaction, while patients who were older (40–64 vs. <40 years: OR: 0.38; 95% CI: 0.19–0.78 and ≥65 vs. <40 years: OR: 0.35; 95% CI: 0.15–0.81), resided in the Caribbean region (OR: 0.48; 95% CI: 0.29–0.81), and had a university education (OR: 0.54; 95% CI: 0.32–0.90) had lower satisfaction. Conclusions: The majority of patients with asthma used pMDIs without an inhalation chamber, and their overall satisfaction was higher than that of patients using other inhalation devices. Patients who received special training from medical specialists showed better satisfaction. [ABSTRACT FROM AUTHOR]

Fernando González-Torralba,1 Adolfo Baloira,2 Araceli Abad,3 Antonia Fuster,4 Juan Luis García-Rivero,5 Patricia García-Sidro,6 Eduardo Márquez-Martín,7 Marta Palop,8 Néstor Soler,9 José Luis Velasco10 1Respiratory Department, University Hospital of Aranjuez, Madrid, Spain; 2Respiratory Department, University Hospital of Pontevedra, Pontevedra, Spain; 3Respiratory Department, University Hospital of Getafe, Madrid, Spain; 4Respiratory Department, University Hospital Son Llatzer, Palma de Mallorca, Spain; 5Respiratory Department, University Hospital Marqués de Valdecilla, Santander, Spain; 6Respiratory Department, University Hospital of La Plana, Castellón, Spain; 7Respiratory Department, University Hospital Virgen del Rocío, Sevilla, Spain; 8Respiratory Department, Hospital of Sagunto, Valencia, Spain; 9Respiratory Department, Hospital Clinic, Barcelona, Spain; 10Respiratory Department, University Hospital Virgen de la Victoria, Málaga, SpainCorrespondence: Adolfo Baloira, Email adolfo.baloira.villar@sergas.esPurpose: The pharmacological treatment of chronic obstructive pulmonary disease (COPD) is largely based on inhaled bronchodilators. Inspiratory flow and lung deposition are key parameters to be considered in inhaled therapy; however, the relationship between these two parameters, the patient specificities, and the suitability of the inhaler type for COPD management has not been fully addressed. The present study follows a Delphi Panel methodology to find expert consensus on the role of inspiratory flow and lung deposition as key decision factors in COPD inhaled therapy.Methods: A two-round Delphi Panel, consisting of 38 statements (items) and completed by 57 Spanish pulmonologists, was carried out to measure the experts’ consensus degree with each item.Results: A high degree of consensus was reached on most of the items consulted, among these inspiratory flow or inspiratory capacity should be periodically considered when choosing an inhalation device and to ensure the suitability of the inhaler used; the outflow velocity and particle size of the different devices should be considered to ensure adequate lung deposition; an active device (pressurized metered-dose inhalers (pMDI) or soft mist inhalers (SMI)) should be used in patients with low inspiratory flow to achieve adequate lung deposition; and, the use of dry powder inhalers (DPI) should be re-evaluated in patients with severe obstruction and severe exacerbations.Conclusion: This study shows the relevance of inspiratory flow and the degree of particle deposition in the lung in the choice of an inhalation device for COPD management, as well as the convenience of an SMI type device in cases of low inspiratory flow. Moreover, it highlights the scarcity of information on the specific features of inhalation devices in COPD guidelines.Keywords: dry powder inhalers, pressurized metered-dose inhalers, soft mist inhaler, inhaled therapy device, exacerbations

Summary: Dry powder inhalers (DPIs) have been well established and recognized for the delivery to the lungs. It provides better drug stability, less irritable, easy to use with deep penetration of drugs in the lungs. Budesonide (BDS) and formoterol fumarate dihydrate (FFD) indicated in pulmonary diseases. The main aim of the study is to evaluate BDS, FFD and their marketed DPIs product in Pakistan were compare in quality and performance with the reference product. The particle size distribution and aerodynamic characterization were analyzed by laser diffraction and multi stage liquid impinger, respectively. The particle density and delivered dose uniformity were also determined. HPLC was also used for the qualitative and quantitative estimation of BDS and FFD along with its marketed products. Laser diffraction particle size analyzer revealed Dv50 53.27 to 56.34 µm having surface area 1815 to 2304 cm3/g. The percentages of emitted dose (%ED) and fine particle fraction (%FPF) was found 98.19 to 99.23% and 31.57 to 34.87%, respectively. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were calculated 2.62 to 2.89 µm and 1.99 to 2.54, correspondingly. The quantitative assay of BDS and FFD in all the commercial DPIs and reference product were well within the pharmacopeial limit i.e. 97.26 to 101.36%. The average of ten units results of delivered dose uniformity for BSD and FFD were also found in the range i.e. 97.97 to 103.19% and 98.48 to 104.41 %, respectively. The results of evaluation of parameters of DPIs like Dv50, %ED, %FPF, MMAD, GSD has shown compliance with the pharmacopeial standards. It is concluded that the all DPIs of BDS/FFD marketed in Pakistan has revealed conformance with the standard of pharmacopoeia and meet the requirements of drug regulatory authority of Pakistan. [ABSTRACT FROM AUTHOR]

Cocrystal engineering is a potent strategy for enhancing drug properties, but its application in spray-drying has been limited. Furthermore, concurrently introducing two drugs and realizing simultaneous pharmacological effects at the target site is challenging. This is particularly evident for oral formulations designed for systemic use, but the local administration of drugs at the target site displays the potential to overcome this problem. Herein, we investigated the potential of cocrystallization principles for use in developing dry powder inhaler formulations of anti-tuberculosis drugs. We focused on the formation of cocrystals of 4-aminosalicylic acid (PAS) and isoniazid (INH), which are crucial components of tuberculosis treatment. Via spray-drying, we successfully produced spray-dried particles of PAS-INH that exhibited hydrogen bonding interactions between the molecules. Aerosolization performance evaluation with an Andersen Cascade Impactor (ACI) confirmed the concurrent deposition of both drugs, highlighting the potential of our particle design for use in the co-delivery of PAS-INH. Furthermore, simulated lung dissolution studies using the ACI and Transwell inserts revealed synchronized dissolution patterns, indicating promising prospects for use in effective drug delivery. This innovative approach to tuberculosis therapy has significant implications for improving treatment efficacy and enhancing patient adherence, potentially revolutionizing tuberculosis treatment. [Display omitted] • PAS-INH cocrystal powder was obtained by spray-drying. • Ternary phase diagram of PAS-INH cocrystal system in solvent was constructed. • Spray-dried cocrystal concurrently deposited on each stage of ACI. • Synchronized dissolution patterns were observed from spray-dried cocrystals. [ABSTRACT FROM AUTHOR]

In this review, an extensive analysis of dry powder inhalers (DPIs) is offered, focusing on their characteristics, formulation, stability, and manufacturing. The advantages of pulmonary delivery were investigated, as well as the significance of the particle size in drug deposition. The preparation of DPI formulations was also comprehensively explored, including physico-chemical characterization of powders, powder processing techniques, and formulation considerations. In addition to manufacturing procedures, testing methods were also discussed, providing insights into the development and evaluation of DPI formulations. This review also explores the design basics and critical attributes specific to DPIs, highlighting the significance of their optimization to achieve an effective inhalation therapy. Additionally, the morphology and stability of 3 DPI capsules (Spiriva, Braltus, and Onbrez) were investigated, offering valuable insights into the properties of these formulations. Altogether, these findings contribute to a deeper understanding of DPIs and their development, performance, and optimization of inhalation dosage forms.

Jill A Ohar,1 Gary T Ferguson,2 Donald A Mahler,3 M Bradley Drummond,4 Rajiv Dhand,5 Roy A Pleasants,4,6 Antonio Anzueto,7 David MG Halpin,8 David B Price,9,10 Gail S Drescher,11 Haley M Hoy,12 John Haughney,9 Michael W Hess,13 Omar S Usmani14 1Section of Pulmonary, Critical Care, Allergy, and Immunology, School of Medicine, Wake Forest University, Winston-Salem, NC, USA; 2Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 3Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 4Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 5Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA; 6Department of Quality, University of Michigan, Ann Arbor, MI, USA; 7Pulmonology Section, University of Texas Health, and South Texas Veterans Health Care System, San Antonio, TX, USA; 8University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 9Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 10Observational and Pragmatic Research Institute, Singapore; 11Pulmonary Services Department, MedStar Washington Hospital Center, Washington, DC, USA; 12Transplant Center, Vanderbilt University Medical Center, Nashville, TN, USA; 13COPD Foundation, Kalamazoo, MI, USA; 14National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, UKCorrespondence: Jill A OharSection of Pulmonary, Critical Care, Allergy, and Immunology, School of Medicine, Wake Forest University, 1834 Wake Forest Road, Winston-Salem, NC 27109, USATel +1 336-716-8426Fax +1 336-716-7277Email johar@wakehealth.eduAbstract: Dry powder inhalers (DPIs) are breath actuated, and patients using DPIs need to generate an optimal inspiratory flow during the inhalation maneuver for effective drug delivery to the lungs. However, practical and standardized recommendations for measuring peak inspiratory flow (PIF)—a potential indicator for effective DPI use in chronic obstructive pulmonary disease (COPD)—are lacking. To evaluate recommended PIF assessment approaches, we reviewed the Instructions for Use of the In-Check™ DIAL and the prescribing information for eight DPIs approved for use in the treatment of COPD in the United States. To evaluate applied PIF assessment approaches, we conducted a PubMed search from inception to August 31, 2021, for reports of clinical and real-life studies where PIF was measured using the In-Check™ DIAL or through a DPI in patients with COPD. Evaluation of collective sources, including 47 applicable studies, showed that instructions related to the positioning of the patient with their DPI, instructions for exhalation before the inhalation maneuver, the inhalation maneuver itself, and post-inhalation breath-hold times varied, and in many instances, appeared vague and/or incomplete. We observed considerable variation in how PIF was measured in clinical and real-life studies, underscoring the need for a standardized method of PIF measurement. Standardization of technique will facilitate comparisons among studies. Based on these findings and our clinical and research experience, we propose specific recommendations for PIF measurement to standardize the process and better ensure accurate and reliable PIF values in clinical trials and in daily clinical practice.Keywords: chronic obstructive pulmonary disease, dry powder inhalers, peak inspiratory flow

BACKGROUND: Inhaled medication is central to the treatment of COPD. Various types of inhaler devices, which directly deliver medication to the lung, have been developed. However, patients often exhibit incorrect techniques of inhaler usage. Effectiveness of therapy may be affected by the ease of device usage, size, convenience of use, durability, clarity of instructions and device preferences of patients. This study compares the satisfaction and preference, as well as error occurrence, with the use of Genuair®, Ellipta™ and Breezhaler™ by healthy subjects in Hong Kong. SUBJECTS AND METHODS: One hundred and thirty healthy Hong Kong Chinese subjects aged ≥40 years without a previous diagnosis of COPD and asthma and with no experience of using dry powder inhalers (DPIs) were recruited. Subjects learned to use the three DPIs by initially reading the instructions and then observing a demonstration with verbal explanation. The number of errors committed was evaluated. Subjects also completed a questionnaire to indicate their satisfaction and preference. RESULTS: The satisfaction score of comfort for Breezhaler was significantly higher than that for Ellipta (p≤0.05), while the satisfaction score on confidence to have inhaled the entire dose was highest for Genuair compared with Ellipta (p≤0.0001) or Breezhaler (p≤0.05). The overall satisfaction score was significantly higher for Genuair than Ellipta (p≤0.05) or Breezhaler (p≤0.01). After reading the instructions, the highest number of subjects committing one or more critical errors was with Breezhaler (97) followed by Genuair (70) and then Ellipta (33). Demonstration reduced the number of critical errors made by subjects for each DPI to one third or lower. CONCLUSION: Breezhaler seemed to be more comfortable and easy to carry, but users made less critical errors when using Ellipta after reading the instructions only. Genuair provided the clearest indication of correct dose preparation and inhalation.

Both the National Heart, Lung, and Blood Institute (NHLBI) and Global Initiative for Asthma (GINA) asthma practice guidelines recommend that providers routinely check inhaler technique and correct any mistakes that patients may make when using these devices. Providers, however, rarely check inhaler technique during asthma visits. The objectives of this study were to: (1) describe the development of an instrument to measure self-efficacy and outcome expectations regarding inhaler technique patient education, (2) evaluate the internal consistency reliability of the new scales, and (3) provide preliminary evidence of construct validity. Methods: First- and second-year physician assistant (PA) students at two institutions completed an anonymous and voluntary survey evaluating two new instruments, the Teaching Inhalers to Patients: Self-efficacy (TIP-SE) and the Teaching Inhalers to Patients: Outcome Expectations (TIP-OE) scales and sociodemographic characteristics. The data were analyzed using Principal Components Analysis (PCA), Cronbach's α, and multivariable logistic regression. Results: We had usable responses from 146 PA students (71.9% participation rate). The PCA identified one factor for the TIP-SE and TIP-OE, respectively. The internal consistency of the TIP-SE and TIP-OE was α = 0.96 and α = 0.92, respectively. The logistic regression found that second-year PA students who had higher mean TIP-SE scores were significantly more likely to report teaching patients to use inhalers during rotations (OR = 1.8, 95% CI = 1.1, 2.9). There was not a statistically significant relationship between reporting teaching patients to use inhalers during rotations and mean TIP-OE scores. Conclusion: The TIP-SE and TIP-OE show preliminary evidence of reliability and validity. Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2008428. [ABSTRACT FROM AUTHOR]

Purpose of Review: Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases that remain uncontrolled in many patients, despite the wide range of therapeutic options available. This review analyzes the available clinical evidence on 3 budesonide/formoterol DPI devices, Spiromax®, Turbuhaler®, and Easyhaler®, in terms of patient-reported outcomes (PROs), inhaler errors, and asthma and COPD control. Recent Findings: The effectiveness of dry powder inhalers (DPI) depends largely on the device and the patient's inhaler technique. Equally important are the patient's perception of the inhaler and adherence. Given the high burden of these diseases, it is important that efforts be made to select the best DPI for each patient and to analyze the impact of these variables to help improve the health and quality of life of our patients. Summary: This review provides a comprehensive overview of the present knowledge about PROs, inhaler handling errors, and asthma and COPD control achieved by Spiromax®, Turbuhaler®, and Easyhaler®. [ABSTRACT FROM AUTHOR]

Context: Management of asthma and chronic obstructive pulmonary disease (COPD) includes use of inhalers as an integral component of drug delivery. Awareness about inhaler devices along with demonstration of the usage of inhaler technique aids in the optimization of therapeutic outcome. Aim: This study aimed to assess the correct use of inhaler technique following pre- and posttraining sessions for the management of COPD and asthma among pulmonary outpatients at a tertiary care hospital. Settings: This prospective cross-sectional study was carried out among patients diagnosed with asthma or COPD and prescribed with inhaler medication in the form of pressurized metered-dose inhaler (pMDI), MDI with spacer, or dry powder inhaler (DPI). Subjects and Methods: The inhaler device use by the patients was assessed initially, followed by a demonstration on inhaler device technique, and reassessed post training using a checklist. Statistical Analysis: Comparison of the median total score of pretraining and posttraining inhaler technique was analyzed by Wilcoxon signed rank test. P < 0.05 was considered statistically significant. Results: Out of 144 patients, 55.6%, 27.7%, and 16.7% of them were prescribed pMDI, MDI with spacer, and DPI, respectively. Post inhaler technique training, about 79.2% of the patients were able to demonstrate the inhaler technique correctly compared to 52.1% prior to training. A statistically significant difference in the median score of inhaler technique has been observed before and after training. Conclusions: This study reports a significant improvement in the correct use of inhaler technique post training. In addition, the most frequent error among inhaler users was revealed to be in the breath actuation. [ABSTRACT FROM AUTHOR]

The goal of this study was to develop an add-on device for dry powder inhalers (Accuhaler) via 3D printing to improve drug administration efficiency in patients with limited inspiratory capacity, including young children, the elderly, and those with chronic obstructive pulmonary disease. With salmeterol xinafoate and fluticasone propionate as model active pharmaceutical ingredients (API), the emitted API doses were used to assess the effectiveness of the add-on device. The APIs were quantified by an HPLC assay validated for specificity, range, linearity, accuracy, and precision. The motor power of the add-on device could be regulated to moderate fan speed and the air flow in the assembled device. When 50–100% of the fan motor power of the add-on device was used, the emitted dose from the attached dry powder inhaler (DPI) was increased. A computational fluid dynamics application was used to simulate the air and particle flow in the DPI with the add-on device in order to elucidate the operating mechanism. The use of the add-on device combined with a sufficient inhalation flow rate resulted in a larger pressure drop and airflow velocity at the blister pocket. As these characteristics are associated with powder fluidization, entrainment, and particle re-suspension, this innovative add-on device might be utilized to enhance the DPI emitted drug dose for patients with low inspiratory rates and to facilitate the provision of adequate drug doses to achieve the treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Inhaler therapy is the most critical route of administering drugs in the management of asthma due to its rapid onset of action, better pulmonary efficacy, and reduced risk of side effects, compared with other routes of administration. Current Concepts: Although many physicians and patients believe they know how to use inhaler devices, most do not know the correct techniques. To achieve better and more effective treatment results, the inhalation device should be appropriate for the characteristics and wishes of each patient. Available inhaler devices include pressurized metered dose inhalers, dry powder inhalers, soft mist inhalers, and nebulizers. To improve disease outcomes and treatment adherence, a personalized stepwise approach, based on each patient's conscious inhalation, inspiratory flow, and hand-lung coordination, is recommended in the selection of the most appropriate device. Discussion and Conclusion: Common problems with inhaler usage include failure to exhale completely before inhaling, insufficient inhalation efforts, and inadequate breath-hold after inhalation. Therefore, continuing education and support are warranted to ensure optimal outcomes and enable patients to improve inhaler usage techniques. Health care providers should also know the devices and develop systems in order to provide comprehensive support to patients in clinical practice. [ABSTRACT FROM AUTHOR]

Inhaled treatments are essential for obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). However, pressurized metered-dose inhalers (pMDI) use propellant gases, contributing to greenhouse gas (GHG) emissions and thereby to climate change. The use of dry powder inhalers (DPI) or soft mist inhalers (SMI) when clinically appropriate is a way to reduce these emissions. It is essential to confirm the diagnosis, promote adherence and therapeutic education, and support effective recycling policies and the development of less polluting treatments. In any case, the right inhaler is the one that suits the patient, is used correctly, and stabilizes of the respiratory condition., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: This study aimed to describe the use of pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) in Spanish subjects in terms of sociodemographic, clinical, and functional characteristics in subjects with asthma or COPD on maintenance treatment with inhaled therapy., Methods: This was a retrospective, descriptive, national, multi-center, and observational study using a database with 1.8 million patients from hospitals and primary care centers as a secondary information source., Results: The sample included 24,102 subjects with asthma on maintenance therapy (26.0% with pMDI, 55% with DPI, and 19.0% with a combination of DPI + pMDI inhalers) and 12,858 subjects with COPD on maintenance therapy (26% with pMDI; 39% with DPI; and 35% with a combination of pMDI + DPI inhalers, mostly extemporary triple therapy). In proportion, subjects ≥ 75 y old used more pMDI than DPI, while younger subjects (40-64 y old) used more DPI. An inhalation chamber was prescribed in 51.0% of subjects with asthma and 47.2% of subjects with COPD treated with pMDI. The use of an inhalation chamber increases with the degree of air-flow limitation by disease and age. In subjects with comorbidities, pMDI inhaler use increased in those ≥ 75 y old for subjects with asthma and subjects with COPD. Switching from pMDI to DPI and vice versa was relatively common: 25% of subjects with asthma and 21.6% of subjects with COPD treated with pMDI had switched from DPI in the previous year. On the contrary, 14.1% and 11.4% of subjects with asthma and subjects with COPD, respectively, treated with DPI had switched from pMDI the last year., Conclusions: The use of pMDI or DPI can vary according to age, both in asthma and COPD. Switching from pMDI to DPI and vice versa is relatively common. Despite the availability of dual- and triple-therapy inhalers on the market, a considerable number of subjects were treated with multiple devices., Competing Interests: Dr Muñoz discloses relationships with AstraZeneca, Boehringer Ingelheim, Chiesi, Faes Farma, Gebro Pharma, GSK, Menarini, Mundipharma, Novartis, Sanofi, and Teva. Dr Re is an employee of Chiesi España. The remaining authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Invasive pulmonary aspergillosis poses a significant threat to immunocompromised patients, characterized by high mortality rates. Posaconazole (PSZ), a second-generation triazole antifungal, exhibits broad-spectrum activity but suffers from limited pulmonary concentrations and notable systemic side effects when administered orally or intravenously. This study focuses on optimizing PSZ nanocrystals-agglomerated particles for dry powder inhalers (DPIs) to enhance solubility, dissolution rates, and pulmonary deposition, ultimately improving therapeutic efficacy while minimizing systemic adverse effects. We employed wet medium milling and spray-drying techniques to formulate PSZ nanocrystals-agglomerated DPIs. Various stabilizers including HPMC, HPC, Soluplus, and PVPK30, were systematically evaluated to optimize physicochemical properties. Aerosolization performance was assessed using the Next Generation Impactor, while antifungal efficacy was evaluated through in vitro and in vivo studies. The optimized PSZ DPIs demonstrated significant enhancements in solubility and dissolution rates, with a fine particle fraction (FPF) of 78.58 ± 3.21%, ensuring optimal lung delivery. In vitro experiments revealed potent effects with minimal cytotoxicity to lung cells. In vivo studies indicated that the optimized formulation achieved a C max /AUC 0→∞ ratio in lung tissues that was 27.32 and 6.76-fold higher than that of the oral suspension, highlighting increased local drug concentrations. This approach presents a scalable, cost-effective strategy for the pulmonary delivery of PSZ, ensuring high drug loading and promising clinical outcomes in treating pulmonary fungal infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)