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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.
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Inaladores de Pó Seco , Manitol , Aerossóis , Pós , Tamanho da Partícula , Administração por InalaçãoRESUMO
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.
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Rifampina , Rifampina/química , Pós/química , Solubilidade , Fenômenos Químicos , Simulação por ComputadorRESUMO
OBJECTIVE: 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. METHODS: A cross-sectional, questionnaire-based survey was conducted. A total of 141 physicians participated and filled the survey. RESULTS: 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. CONCLUSIONS: 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.
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Asma , Médicos , Doença Pulmonar Obstrutiva Crônica , Humanos , Asma/tratamento farmacológico , Estudos Transversais , Nepal , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Terapia Respiratória , Inaladores Dosimetrados , Inaladores de Pó Seco , Inquéritos e Questionários , Percepção , Administração por InalaçãoRESUMO
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.
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Lesão Pulmonar Aguda , Benzilisoquinolinas , COVID-19 , Ratos , Animais , Administração por Inalação , Inaladores de Pó Seco , COVID-19/metabolismo , SARS-CoV-2 , Aerossóis e Gotículas Respiratórios , Pulmão/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Benzilisoquinolinas/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/análise , Tamanho da Partícula , Pós/análiseRESUMO
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder that affects millions of people worldwide and inhalation therapy is central to the symptomatic management of the disease. Therefore, knowledge of the minimum Peak inspiratory flow (PIF) requirements for specific inhalers especially dry powder inhalers (DPI's) is necessary when prescribing inhalation therapy. The purpose of this study is to assess the effect of COPD severity on PIF in patients with COPD. METHODOLOGY: A total of 150 subjects (75 patients with stable COPD, and 75 apparently healthy subjects) participated in the study. PIF was assessed using the In-check Inhaler Assessment Kit (manufactured by Clement Clarke International Ltd, Harlow, UK). Lung function was assessed by spirometry with subjects divided into four groups based on the severity of their airway obstruction using the GOLD criteria. The Modified Medical Research Council (MMRC) dyspnea scale was used to assess dyspnea severity. Exercise capacity was assessed using the 6-minute walk test. Statistical analysis was performed with SPSS 23.0 software. In all the statistical tests, a p value of <0.05 was considered significant. RESULTS: The mean age for the COPD patient and control population are 72.48 ± 8.01 and 70.69 ± 5.82 respectively. The control group had higher PIF than COPD group; however, only the clickhler and pMDI had statistically significant difference between the mean PIF of the patients compared with the control group. Generally, there was an observed trend of a decrease in mean PIF as the COPD stage progresses with a statistically significant difference observed for Easibreathe (F= 3.52, p= 0.019) and pressurized Metered dose inhaler (pMDI) (F= 4.26, p= 0.008). There was a significant positive correlation between FEV1%, FVC, Exercise capacity (6-minute walk distance) and PIF for Clickhaler, Autohaler, Easybreathe and pMDI. For pMDI, there was a statistically significant difference between means of PIF across the MMRC dyspnea scale with PIF decreasing with increasing severity of dyspnea (F= 2.85, p= 0.033). CONCLUSION: COPD patients have slightly lower PIF than controls. Poor exercise tolerance and lower spirometric pulmonary function parameters may contribute to low PIF.
INTRODUCTION: La bronchopneumopathie chronique obstructive (BPCO) est un trouble respiratoire chronique qui touche des millions de personnes dans le monde et la thérapie par inhalation est essentielle à la gestion symptomatique de la maladie. Par conséquent, il est nécessaire de connaître les exigences minimales en matière de débit inspiratoire de pointe (DIP) pour certains inhalateurs, en particulier les inhalateurs de poudre sèche (IPS), lors de la prescription d'un traitement par inhalation. L'objectif de cette étude est d'évaluer l'effet de la gravité de la BPCO sur le débit de pointe inspiratoire chez les patients atteints de BPCO. MÉTHODOLOGIES: Un total de 150 sujets (75 patients atteints de BPCO stable et 75 sujets apparemment sains) ont participé à l'étude. Le PIF a été évalué à l'aide du kit d'évaluation In-check Inhaler (fabriqué par Clement Clarke International Ltd, Harlow, UK). La fonction pulmonaire a été évaluée par spirométrie, les sujets étant répartis en quatre groupes en fonction de la gravité de l'obstruction des voies respiratoires selon les critères GOLD. L'échelle de dyspnée modifiée du Medical Research Council (MMRC) a été utilisée pour évaluer la sévérité de la dyspnée. La capacité d'exercice a été évaluée à l'aide du test de marche de 6 minutes. L'analyse statistique a été réalisée avec le logiciel SPSS 23.0. Dans tous les tests statistiques, une valeur p de <0,05 a été considérée comme significative. RÉSULTATS: L'âge moyen des patients atteints de BPCO et de la population de contrôle est respectivement de 72,48 ± 8,01 et 70,69 ± 5,82. Le groupe de contrôle avait un PIF plus élevé que le groupe BPCO; cependant, seuls le clickhler et le pMDI présentaient une différence statistiquement significative entre le PIF moyen des patients et celui du groupe de contrôle. D'une manière générale, on a observé une tendance à la diminution du FRP moyen au fur et à mesure de l'évolution de la BPCO, avec une différence statistiquement significative pour l'Easibreathe (F= 3,52, p= 0,019) et l'aérosol-doseur pressurisé (pMDI) (F= 4,26, p= 0,008). Il existe une corrélation positive significative entre le VEMS, la CVF, la capacité d'exercice (distance de marche de 6 minutes) et le PIF pour Clickhaler, Autohaler, Easybreathe et pMDI. Pour le pMDI, il y avait une différence statistiquement significative entre les moyennes de PIF sur l'échelle de dyspnée du MMRC, le PIF diminuant avec l'augmentation de la sévérité de la dyspnée (F= 2,85, p= 0,033). CONCLUSION: Les patients atteints de BPCO ont un PIF légèrement inférieur à celui des témoins. Une mauvaise tolérance à l'exercice et des paramètres spirométriques de la fonction pulmonaire plus faibles peuvent contribuer à la faiblesse du PIF. Mots clés: Maladie pulmonaire obstructive chronique, Inhalateurs de poudre sèche, Débit inspiratoire de pointe, Aérosol-doseur pressurisé.
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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 2±1.6, single-dose powder inhaler -1.5±1.3, multiple-dose dry powder inhaler - 1.25±1.4, soft-mist inhaler - 0.68±0.7 (Ñ=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 (Ñ=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.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Feminino , Estudos Transversais , Desenho de Equipamento , Asma/diagnóstico , Asma/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Nebulizadores e Vaporizadores , Administração por Inalação , Inaladores de Pó Seco , Dispneia/diagnóstico , Dispneia/etiologiaRESUMO
Dry powder inhalers (DPIs) are a large, highly diverse group of inhalation devices. DPIs differentiate the process of measuring the dose of the drug and preparing the inhaler for use, but also the way of transmitting and the scope of feedback on the inhalation process that the user receives. The functioning of simple and technologically advanced systems of feedback on the inhalation process in the most commonly used multi-dose DPIs is discussed. All these DPIs have a dose counter. Only three DPIs - Novolizer®, Genuair® and NEXThaler® provide feedback to the patient in the form of auditory and visual signals confirming the correctness of the inhalation performed. This is important for the correct use of the inhaler, and thus for obtaining the expected therapeutic effects.
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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. 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®.
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Asma , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Inaladores de Pó Seco , Humanos , Medidas de Resultados Relatados pelo Paciente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de VidaRESUMO
INTRODUCTION: 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 .
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Asma , Administração por Inalação , Asma/tratamento farmacológico , Humanos , Inaladores Dosimetrados , Motivação , Nebulizadores e Vaporizadores , Psicometria , Reprodutibilidade dos Testes , AutoeficáciaRESUMO
Despite the fact that capsules play an important role in many dry powder inhalation (DPI) systems, few studies have been conducted to investigate the capsules' interactions with respirable powders. The effect of four commercially available hydroxypropyl methylcellulose (HPMC)inhalation-grade capsule types on the aerosol performance of two model DPI formulations (lactose carrier and a carrier-free formulation) at two different pressure drops was investigated in this study. There were no statistically significant differences in performance between capsules by using the carrier-based formulation. However, there were some differences between the capsules used for the carrier-free rifampicin formulation. At 2-kPa pressure drop conditions, Embocaps® VG capsules had a higher mean emitted fraction (EF) (89.86%) and a lower mean mass median aerodynamic diameter (MMAD) (4.19 µm) than Vcaps® (Capsugel) (85.54%, 5.10 µm) and Quali-V® I (Qualicaps) (85.01%, 5.09 µm), but no significant performance differences between Embocaps® and ACGcaps™ HI. Moreover, Embocaps® VG capsules exhibited a higher mean respirable fraction (RF)/fine particle fraction (FPF) with a 3-µm-sized cutoff (RF/FPF< 3 µm) (33.05%/35.36%) against Quali-V® I (28.16%/31.75%) (P < 0.05), and a higher RF/FPF with a 5-µm-sized cutoff (RF/FPF< 5 µm) (49.15%/52.57%) versus ACGcaps™ HI (38.88%/41.99%) (P < 0.01) at 4-kPa pressure drop condition. Aerosol performance variability, pierced-flap detachment, as well as capsule hardness and stiffness, may all influence capsule type selection in a carrier-based formulation. The capsule type influenced EF, RF, FPF, and MMAD in the carrier-free formulation.
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Budesonida , Rifampina , Administração por Inalação , Aerossóis , Cápsulas , Química Farmacêutica , Inaladores de Pó Seco , Derivados da Hipromelose , Tamanho da Partícula , PósRESUMO
Carriers play an important role in improving the aerosolization performance of dry powder inhalers (DPIs). Despite that intensive attention had been paid to the establishment of the advanced carriers with controllable physicochemical properties in recent years, the design and optimization of carrier-based DPIs remain an empiricism-based process. DPIs are a powder system of complex multiphase, and thus their physicochemical properties cannot fully explain the powder behavior. A comprehensive exposition of powder properties is demanded to build a bridge between the physicochemical properties of carriers and the aerosolization performance of DPIs. In this study, an FT-4 powder rheometer was employed to explore the powder properties, including dynamic flow energy, aeration, and permeability of the chitosan-mannitol binary carriers (CMBCs). CMBCs were self-designed as an advanced carrier with controllable surface roughness to obtain enhanced aerosolization performance. The specific mechanism of CMBCs to enhance the aerosolization performance of DPIs was elaborated based on the theory of pulmonary delivery processes by introducing powder properties. The results exhibited that CMBCs with appropriate surface roughness had lower special energy, lower aeration energy, and higher permeability. It could be predicted that CMBC-based DPIs had greater tendency to fluidize and disperse in airflow, and the lower adhesion force between particles enabled drugs to be detached from the carrier to achieve higher fine particle fractions. The specific mechanism on how physicochemical properties influenced the aerosolization performance during the pulmonary delivery processes could be figured out with the introduction of powder properties.
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Quitosana , Inaladores de Pó Seco , Administração por Inalação , Aerossóis/química , Portadores de Fármacos/química , Excipientes/química , Manitol/química , Tamanho da Partícula , Pós/químicaRESUMO
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.
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COVID-19 , Vacinas Virais , Humanos , Vacinas contra COVID-19 , Síndrome da Liberação de Citocina , Pandemias/prevenção & controle , COVID-19/prevenção & controle , SARS-CoV-2 , PulmãoRESUMO
BACKGROUND: Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) are commonly used drug-delivering devices for patients with chronic airway diseases. Appropriate peak inhalation flow rate (PIFR) and inhaler technique is essential for effective therapy. We aimed at optimizing inhalation therapy through the analysis of PIFRs in patients with chronic obstructive pulmonary disease (COPD) or asthma as well as the effect of technique training using In-Check DIAL® to help patients to achieve their optimal inspiratory flow rates. METHODS: The study continuously enrolled patients who were diagnosed as COPD or asthma from respiratory clinics. PIFRs were described and analyzed between the newly-diagnosed and follow-up patients, and the stable and acute exacerbation patients, respectively. Every participant was trained inhaler technique using In-Check DIAL®. PIFRs before and after training was compared by self-control analysis. RESULTS: Among a total of 209 patients, the average age was 56.9 years. For DPIs users, 10.8% patients had a PIFR < 30 L/min and 44.1% patients had a PIFR ≥ 60 L/min before technique training. After technique training, scarcely patient (1.5%) had a PIFR < 30 L/min, and 60.5% patients had a PIFR ≥ 60 L/min. The patient's average PIFR increased by 5.6L/min after training. The increase in PIFR before and after training was significant (p < 0.001) for most patients, but no significant variation was found in patients with acute exacerbation (p = 0.822). CONCLUSIONS: A considerable number of patients with COPD or asthma were not able to achieve the minimum or optimal PIFR for DPIs. Inhaler training can increase patients' PIFRs and improve their ability to use DPIs. Trail registration The study has registered in chictr.org.cn (ChiCTR1900024707) and been approved by the Ethics Committee of Zhongshan Hospital of Fudan University (B2019-142).
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Asma/tratamento farmacológico , Inaladores de Pó Seco , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Terapia Respiratória , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Estudos ProspectivosRESUMO
BACKGROUND: Inhaler selection is important when managing respiratory conditions; a patient's inhalation technique should be appropriate for the selected device, and patients should ideally be able to use a device successfully regardless of disease severity. The NEXThaler is a multidose dry-powder inhaler with a breath-actuated mechanism (BAM) and dose counter that activates only following inhalation, so effectively an 'inhalation counter'. We assessed inspiratory flow through the NEXThaler in two studies and examined whether inhalation triggered the BAM. METHODS: The two studies were open-label, single-arm, and single visit. One study recruited patients with asthma aged ≥ 18 years; the other recruited patients with chronic obstructive pulmonary disease (COPD) aged ≥ 40 years. All patients inhaled twice through a placebo NEXThaler. The inspiratory profile through the device was assessed for each inhalation using acoustic monitoring, with flow at and time to BAM firing, peak inspiratory flow (PIF), and total inhalation time assessed. RESULTS: A total of 40 patients were enrolled in the asthma study: 20 with controlled asthma and 20 with partly controlled/uncontrolled asthma. All patients were able to trigger the BAM, as evidenced by the inhalation counter activating on closing the device. Mean flow at BAM firing following first inhalation was 35.0 (range 16.3-52.3) L/min; mean PIF was 64.6 (35.0-123.9) L/min. A total of 72 patients were enrolled in the COPD study, with data analysed for 69 (mean forced expiratory volume in 1 s 48.7% predicted [17-92%]). As with the asthma study, all patients, regardless of airflow limitation, were able to trigger the BAM. Mean flow at BAM firing following first inhalation was 41.9 (26.6-57.1) L/min; mean PIF was 68.0 (31.5-125.4) L/min. Device usability was rated highly in both studies, with 5 min sufficient to train the patients, and a click heard shortly after inhalation in all cases (providing feedback on BAM firing). CONCLUSIONS: Inhalation flows triggering the BAM in the NEXThaler were similar between patients with controlled and partly controlled/uncontrolled asthma, and were similar across COPD airflow limitation. All enrolled patients were able to activate the device.
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Asma/fisiopatologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Terapia Respiratória/instrumentação , Terapia Respiratória/métodos , Administração por Inalação , Adolescente , Adulto , Idoso , Asma/terapia , Inaladores de Pó Seco , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/terapia , Testes de Função Respiratória , Adulto JovemRESUMO
The de-agglomeration characteristics of single agglomerate-wall impaction are examined using high-resolution shadowgraph imaging. Experiments are performed to investigate the effects of constituent particle size (D 50 from 3-7 µ m) and air velocity on the individual size and velocity of de-agglomerated fragments at conditions relevant to dry powder inhalation systems. De-agglomerated fragment area and trajectories were used to differentiate between pseudo-elastic and inelastic collisions during de-agglomeration. Advanced image processing techniques have enabled provision of joint population distributions of fragment area and aspect ratio, which identify a bimodal dispersion of fragments during de-agglomeration. The bimodality is destroyed with increasing air velocity and also generally diminishes with time after impact. The experiment presented forms a platform for the detailed quantitative characterisation of de-agglomeration behaviour and can be useful towards the development and validation of related computational models for pharmaceutical dry powder inhalers.
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We performed a cross-sectional study within a specialised respiratory inpatient unit assessing 25 nurses' [85% female, 8.0 ± 7.9 (mean ± SD) years' experience in nursing] confidence in providing inhaler device education using a self-reported questionnaire, and their competency (% correct steps) in using eight different inhaler devices. Sixteen percent of participants were 'not confident' providing inhaler education, while 84% were 'moderately' or 'extremely' confident. The mean (±SD)% correct steps for all devices was 47 ± 17%. There was no correlation between % correct steps and nursing years (r = 0.21, p = 0.31), or 'confidence' with providing inhaler education (r = 0.02, p = 0.91) but % correct steps strongly correlated with number of individual device prescriptions within the hospital in the preceding year (r = 0.78, p = 0.039). Most respiratory nurses felt confident in teaching inhaler technique but their overall demonstrated ability to correctly use inhalers was poor, especially for less frequently prescribed devices within our hospital. Regular assessment and ongoing education on correct inhaler technique for respiratory nurses is necessary to optimise all device usage by nurses, irrespective of experience or confidence.
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Enfermeiras e Enfermeiros , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Estudos Transversais , Feminino , Humanos , Pacientes Internados , Masculino , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Inquéritos e QuestionáriosRESUMO
Respiratory diseases are among the leading causes of morbidity and mortality worldwide. Innovations in biochemical engineering and understanding of the pathophysiology of respiratory diseases resulted in the development of many therapeutic proteins and peptide drugs with high specificity and potency. Currently, protein and peptide drugs are mostly administered by injections due to their large molecular size, poor oral absorption, and labile physicochemical properties. However, parenteral administration has several limitations such as frequent dosing due to the short half-life of protein and peptide in blood, pain on administration, sterility requirement, and poor patient compliance. Among various noninvasive routes of administrations, the pulmonary route has received a great deal of attention and is a better alternative to deliver protein and peptide drugs for treating respiratory diseases and systemic diseases. Among the various aerosol dosage forms, dry powder inhaler (DPI) systems appear to be promising for inhalation delivery of proteins and peptides due to their improved stability in solid state. This review focuses on the development of DPI formulations of protein and peptide drugs using advanced spray drying. An overview of the challenges in maintaining protein stability during the drying process and stabilizing excipients used in spray drying of proteins and peptide drugs is discussed. Finally, a summary of spray-dried DPI formulations of protein and peptide drugs, their characterization, various DPI devices used to deliver protein and peptide drugs, and current clinical status are discussed.
Assuntos
Peptídeos Catiônicos Antimicrobianos/síntese química , Composição de Medicamentos/métodos , Inaladores de Pó Seco/métodos , Proteínas Recombinantes/síntese química , Secagem por Atomização , Administração por Inalação , Aerossóis/química , Animais , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Dessecação/métodos , Excipientes/química , Humanos , Isoleucina/administração & dosagem , Isoleucina/síntese química , Manitol/administração & dosagem , Manitol/síntese química , Tamanho da Partícula , Peptídeos , Pós/química , Proteínas Recombinantes/administração & dosagemRESUMO
Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa. The purpose of this study was to develop dry powder inhaler formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water-insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs). Inhalable composite microparticles of Iva-BSA-NPs were produced by spray-freeze-drying using water-soluble Col as the matrix material and l-leucine as an aerosol enhancer. The optimal formulation showed an irregularly shaped morphology with fine particle fraction (FPF) values of 73.8 ± 5.2% for Col and 80.9 ± 4.1% for Iva. Correlations between "D×ρtapped" and FPF were established for both Iva and Col. The amorphous solubility of Iva is 66 times higher than the crystalline solubility in the buffer. Iva-BSA-NPs were amorphous and remained in the amorphous state after spray-freeze-drying, as examined by powder X-ray diffraction. In vitro dissolution profiles of the selected DPI formulation indicated that Col and Iva were almost completely released within 3 h, which was substantially faster regarding Iva release than the jet-milled physical mixture of the two drugs. In summary, this study developed a novel inhalable nanocomposite microparticle using a synergistic water-soluble drug as the matrix material, which achieved reduced use of excipients for high-dose medications, improved dissolution rate for the water-insoluble drug, and superior aerosol performance.
Assuntos
Aerossóis/química , Nanocompostos/química , Solubilidade/efeitos dos fármacos , Administração por Inalação , Aerossóis/farmacologia , Aminofenóis/química , Aminofenóis/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Colistina/química , Colistina/farmacologia , Composição de Medicamentos/métodos , Inaladores de Pó Seco/métodos , Excipientes/química , Nanopartículas/química , Tamanho da Partícula , Pós/química , Pós/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Quinolonas/química , Quinolonas/farmacologiaRESUMO
PURPOSE: A combined in vitro - in silico methodology was designed to estimate pharmacokinetics of budesonide delivered via dry powder inhaler. METHODS: Particle size distributions from three budesonide DPIs, measured with a Next Generation Impactor and Alberta Idealized Throat, were input into a lung deposition model to predict regional deposition. Subsequent systemic exposure was estimated using a pharmacokinetic model that incorporated Nernst-Brunner dissolution in the conducting airways to predict the net influence of dissolution, mucociliary clearance, and absorption. RESULTS: DPIs demonstrated significant in vitro differences in deposition, resulting in large differences in simulated regional deposition in the central conducting airways and the alveolar region. Similar but low deposition in the small conducting airways was observed with each DPI. Pharmacokinetic predictions showed good agreement with in vivo data from the literature. Peak systemic concentration was tied primarily to the alveolar dose, while the area under the curve was more dependent on the total lung dose. Tracheobronchial deposition was poorly correlated with pharmacokinetic data. CONCLUSIONS: Combination of realistic in vitro experiments, lung deposition modeling, and pharmacokinetic modeling was shown to provide reasonable estimation of in vivo systemic exposure from DPIs. Such combined approaches are useful in the development of orally inhaled drug products.
Assuntos
Broncodilatadores/administração & dosagem , Broncodilatadores/farmacocinética , Budesonida/administração & dosagem , Budesonida/farmacocinética , Inaladores de Pó Seco/instrumentação , Administração por Inalação , Broncodilatadores/sangue , Budesonida/sangue , Simulação por Computador , Desenho de Equipamento , Humanos , Técnicas In Vitro , Pulmão/fisiologia , Modelos Biológicos , Tamanho da Partícula , Faringe , Equivalência TerapêuticaRESUMO
Respiratory tract is one of the oldest routes for drug delivery. It can be used for local and systemic drug deliveries. Inhalation therapy has several advantages over oral. It delivers the drug efficiently to the lung with minimal systemic exposure, thus avoiding systemic side effects common with oral route. In this review, different types of inhaler devices are illustrated like metered dose inhalers (MDIs), dry powder inhalers (DPIs), nebulizers, and the new soft mist inhalers (SMIs). Since dry powder is more stable than when in liquid form, we will discuss in detail DPIs highlighting different techniques utilized in preparation of dry powders with or without carrier to improve flowability and drug delivery to deep lungs. Types of DPIs are briefly discussed with examples from the market. Several mechanisms for particle deposition are mentioned with factors governing the process. Pharmacokinetic profile of the inhaled particles is detailed starting from the dissolution, followed by the rapid absorption and ending with systemic clearance. New technologies like 3D printing in pulmonary field are also highlighted.