Numerical simulation of emitted particle characteristics and airway deposition distribution of Symbicort® Turbuhaler® dry powder fixed combination aerosol drug

Farkas, Árpád; Jókay, Ágnes; Balásházy, Imre; Füri, Péter; Müller, Veronika; Tomisa, Gábor; Horváth, Alpár

doi:10.1016/j.ejps.2016.08.036

Cited by 28 publications

(21 citation statements)

References 51 publications

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“…Earlier versions dealt with constant inspiratory and expiratory flow rates based on the inhaled/exhaled volume and inhalation and exhalation times. The deposition model has been earlier validated based on experimental scintigraphic deposition data (see Farkas et al, 2016). Since in this work the model was applied to compute the deposition of Foster ® NEXThaler ® drug particles, present validation process consisted in comparing our theoretical deposition results with deposition data of Foster ® NEXThaler ® yielded by the scintigraphic experiments of Mariotti …”

Section: Description Of the Computational Methodsmentioning

confidence: 99%

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler

Farkas

Lewis

Church

et al. 2017

International Journal of Pharmaceutics

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Link to publication record in Explore Bristol Research PDF-document This is the final published version of the article (version of record). It first appeared online via Elsevier at https://www.sciencedirect.com/science/article/pii/S0378517317309237 . Please refer to any applicable terms of use of the publisher. University of Bristol -Explore Bristol Research General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms A B S T R A C TThe breath-actuated mechanism (BAM) is a mechanical unit included in NEXThaler ® with the role of delaying the emission of the drug until the inhalation flow rate of the patient is sufficiently high to detach the drug particles from their carriers.The main objective of this work was to analyse the effect of the presence of BAM on the size distribution of the emitted drug and its airway deposition efficiency and distribution. Study of the hygroscopic growth of the emitted drug particles and its effect on the deposition was another goal of this study.Size distributions of Foster ® NEXThaler ® drug particles emitted by dry powder inhalers with and without BAM have been measured by a Next Generation Impactor. Three characteristic inhalation profiles of asthmatic patients (low, moderate and high flow rates) were used for both experimental and modelling purposes. Particle hygroscopic growth was determined by a new method, where experimental measurements are combined with simulations. Upper airway and lung deposition fractions were computed assuming 5 s and 10 s breath-hold times.By the inclusion of BAM the fine particle fraction of the steroid component increased from 24 to 30% to 47-51%, while that of bronchodilator from 25-34% to 52-55%. The predicted upper airway steroid and bronchodilator doses decreased from about 60% to 35-40% due to BAM. At the same time, predicted lung doses increased from about 20%-35% (steroid) and from 22% to 38% (bronchodilator) for the moderate flow profile and from about 25% to 40% (steroid) and from 29% to 47% (bronchodilator) for the high inhalation flow profile. Although BDP and FF upper airway doses decreased by a factor of about two when BAM was present, lung doses of both components were about the same in the BAM and no-BAM configurations at the weakest flow profile. However, lung dose increased by 2-3% even for this profile when hygroscopic growth was taken into account.In conclusion, the NEXThaler ® BAM mechanism is a unique feature enabling high emitted fine particle fraction and enhanced drug delivery to the lungs.

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Section: Description Of the Computational Methodsmentioning

confidence: 99%

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler

Farkas

Lewis

Church

et al. 2017

International Journal of Pharmaceutics

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“…The numerical deposition model was validated for the case of medical aerosols in our earlier works (e.g. Farkas et al 2016;Farkas et al 2017). The inputs of the model were the size distributions of the drugs measured in this work by cascade impactor techniques and the inhalation profile of a COPD patient when inhaling through Breezhaler ® derived from the work (Colthorpe et al 2013).…”

Section: In Silico Stochastic Modelmentioning

confidence: 99%

Novel dry powder inhaler formulation containing antibiotic using combined technology to improve aerodynamic properties

Ambrus

Benke

Farkas

et al. 2018

European Journal of Pharmaceutical Sciences

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Dry Powder Inhaler (DPI) could offer a propellant-free, easy-to-use powder form ensuring better stability than liquid dosage forms. Therefore the development of traditional carrier-based and carrier-free new generation systems is a determinative factor in the field of DPI formulation. The purpose of our research work was to combine these two systems, utilizing their beneficial properties to produce a novel pulmonary drug delivery system containing ciprofloxacin hydrochloride (CIP). Co-spray drying, surface smoothing and the preparation of an interactive physical mixture were applied as the technological procedures of sample preparation. The carrier-based and carrier-free formulations, as well as the developed novel product were compared to each other. Structural investigations were made by X-ray powder diffraction and micrometric properties (habit, bulk density) were determined. Particle interactions were also evaluated to investigate surface free energy, cohesive-adhesive forces, and spreading coefficient. In vitro aerodynamic properties (mass median aerodynamic diameter), fine particle fraction (FPF) and emitted dose of DPIs were measured using Andersen Cascade Impactor. A novel in silico Stochastic Lung Model was also used to quantify the amount of particles deposited at the target area. The novel-formulated composition presented amorphous spherical particles with an average size of about 2 μm. The in vitro aerodynamic investigations showed a variance in FPF as a function of formulation method (carrier-based: 24%, carrier-free: 54% and applying the novel combination method: 63%). The in silico deposition results were in line with the in vitro measurements and yielded increased lung doses for the sample prepared by the combined technology. This novel DPI formulation provides an opportunity for a more effective therapy with deeper deposition of CIP.

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“…(12,30) The most important breath profile parameters influencing pulmonary drug deposition include IVC d , PIF d , and t in . (17,31) Inhalation parameters have an impact on fine-particle fraction, mass median aerodynamic diameter (MMAD), as well as on emitted dose, especially in DPIs. (17,31) MMAD can be determined by measurements with a cascade impactor at different flow rates and is highly influenced by PIF.…”

Section: Discussionmentioning

confidence: 99%

The Repeatability of Inspiration Performance Through Different Inhalers in Patients with Chronic Obstructive Pulmonary Disease and Control Volunteers

Erdélyi

Lázár

Odler

et al. 2020

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: Inhalation therapy is a cornerstone of treating patients with chronic obstructive pulmonary disease (COPD). Inhaler types and through-device inhalation parameters influence airway drug delivery. We aimed to measure the repeatability of inhalation performance through four different commercially available inhalers. Methods: We recruited control subjects (n ¼ 22) and patients with stable COPD (S-COPD, n ¼ 16) and during an acute exacerbation (AE-COPD, n ¼ 15). Standard spirometry was followed by through-device inhalation maneuvers using Ellipta Ò , Evohaler Ò , Respimat Ò , and Genuair Ò. Through-device inspiratory vital capacity (IVC d) and peak inspiratory flow (PIF d), as well as inhalation time (t in) and breath hold time (t bh), were recorded and all measurements were repeated in a random manner. Results: There was no difference in forced expiratory volume in 1 second (FEV 1) between patients (S-COPD: 39-5 vs. AE-COPD: 32%-5% predicted, p > 0.05). In controls, the IVC d was significantly reduced by all four devices in comparison with the slight reduction seen in COPD patients. In all subjects, PIF was lowered when inhaling through the devices in order of decreasing magnitude in PIF d : Evohaler, Respimat, Ellipta, and Genuair. The Bland-Altman analysis showed a highly variable coefficient of repeatability for IVC d and PIF d through the different inhalers for all COPD patients. Based on the intermeasurement differences in patients, Respimat and Genuair showed the highest repeatability for IVC d , while Genuair and Ellipta performed superior with regard to PIF d. Conclusions: Our study is the first to compare repeatability of inhalation performances through different inhalers in COPD patients, showing great individual differences for parameters influencing lung deposition of inhaled medication from a given device. Our data provide new insight into the characterization of inhaler use by patients with COPD, and might aid the selection of the most appropriate devices to ensure the adequate and consistent delivery of inhaled drugs.

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Numerical simulation of emitted particle characteristics and airway deposition distribution of Symbicort® Turbuhaler® dry powder fixed combination aerosol drug

Cited by 28 publications

References 51 publications

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler

Novel dry powder inhaler formulation containing antibiotic using combined technology to improve aerodynamic properties

The Repeatability of Inspiration Performance Through Different Inhalers in Patients with Chronic Obstructive Pulmonary Disease and Control Volunteers

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