Multivariate Analysis of Effects of Asthmatic Patient Respiratory Profiles on the In Vitro Performance of a Reservoir Multidose and a Capsule-Based Dry Powder Inhaler

Buttini, Francesca; Pasquali, Irene; Brambilla, G.; Copelli, Diego; Alberi, Massimiliano Dagli; Balducci, Anna; Bettini, Ruggero; Sisti, Viviana

doi:10.1007/s11095-015-1820-1

Cited by 11 publications

(3 citation statements)

References 21 publications

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“…In vitro dose emission studies focus on identifying the optimal inhalation flow rate for dose deaggregation; however, this optimal flow may not be achievable in real-life use by the patient. The multivariate statistical approach study carried out by Buttini et al demonstrates that the fine particle mass emitted from the single-dose inhaler device has significantly decreased when the minimum inspiratory volume was used to operate the device (18). The information that is most clinically relevant is to identify the type of dose emitted when low inhalation flows and inhaled volumes are used.…”

Section: Introductionmentioning

confidence: 99%

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

et al. 2017

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Abstract.Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.

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Section: Introductionmentioning

confidence: 99%

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

et al. 2017

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“…This ensures that the air flow has accelerated sufficiently and reduces the dependence of delivered drug dose on a patient's inspiratory effort. Buttini et al (2015) and Buttini et al (2016) considered this issue and produced a significant dataset to confirm that the performance of the Nexthaler® device was insensitive to applied air flow rate.…”

Section: Discussionmentioning

confidence: 99%

Optical diagnostics studies of air flow and powder fluidisation in Nexthaler®. Part II: Use of fluorescent imaging to characterise transient release of fines from a dry powder inhaler

Merusi

Brambilla

Long

et al. 2018

International Journal of Pharmaceutics

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The fine particle fraction is a key indicator of therapeutic effectiveness of inhaled pharmaceutical aerosols. This paper presents a fluorescence imaging technique to visualise and characterise the emission of active pharmaceutical ingredient (API) fines in model formulations containing coarse lactose carrier and 1.5-2 μm diameter fluorescent microspheres (model API fines). A two-camera arrangement was used to acquire simultaneous images of spatial and temporal distribution of model API fines and fluidised powder formulation near the mouthpiece exit of a DPI. Digital image analysis showed that the model API fines were released along with the bulk of the powder dose. More rapidly accelerating airflows were found to cause earlier release of API fines. The fluorescence imaging technique analyses a substantial fraction of the aerosol plume and was found to provide effective time-resolved characterisation of the de-aggregation and release of API fines with consistent results across a wide range of model API concentrations. Future studies should demonstrate the usefulness of the fluorescence imaging technique across different formulations and DPI devices.

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“…If the inhalation was not successful, for example if the patient did not generate sufficient inspiratory flow, just exhaled through the device, or only opened and closed the cover, the counter will not count down, and the dose is not wasted. Data on dose- and flow-independency of the NEXThaler across various inspiratory flows have previously been published [ 7 , 8 ], as have lung deposition [ 9 ] and usability data [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Inspiratory flow profile and usability of the NEXThaler, a multidose dry powder inhaler, in asthma and COPD

et al. 2021

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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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Multivariate Analysis of Effects of Asthmatic Patient Respiratory Profiles on the In Vitro Performance of a Reservoir Multidose and a Capsule-Based Dry Powder Inhaler

Cited by 11 publications

References 21 publications

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

Optical diagnostics studies of air flow and powder fluidisation in Nexthaler®. Part II: Use of fluorescent imaging to characterise transient release of fines from a dry powder inhaler

Inspiratory flow profile and usability of the NEXThaler, a multidose dry powder inhaler, in asthma and COPD

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