<i>In Vitro</i> Testing of Two Formoterol Dry Powder Inhalers at Different Flow Rates

Weuthen, Thomas; Roeder, S.; Brand, Peter; Müllinger, B.; Scheuch, G.

doi:10.1089/089426802760292636

Cited by 44 publications

(24 citation statements)

References 16 publications

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“…When using a DPI, this is counterbalanced by the flow-dependent dose emission from a DPI. However, dose emission from an Aerolizer (35) and a Diskus (20) is less flow-dependent than that from other DPIs. Hence, the low resistance of these devices, together with the resultant fast inhalation flows, will tend to provide low lung deposition and high oropharyngeal impaction.…”

Section: Dry Powder Inhaler Inhalation Maneuversmentioning

confidence: 96%

The Inhalation Characteristics of Patients When They Use Different Dry Powder Inhalers

Azouz

Chetcuti

Hosker

et al. 2015

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: The characteristics of each inhalation maneuver when patients use dry powder inhalers (DPIs) are important, because they control the quality of the emitted dose. Methods: We have measured the inhalation profiles of asthmatic children [CHILD; n¼16, mean forced expiratory volume in 1 sec (FEV 1 ) 79% predicted], asthmatic adults (ADULT; n¼53, mean predicted FEV 1 72%), and chronic obstructive pulmonary disease (COPD; n¼29, mean predicted FEV 1 42%) patients when they inhaled through an Aerolizer, Diskus, Turbuhaler, and Easyhaler using their ''real-life'' DPI inhalation technique. These are low-, medium-, medium/high-, and high-resistance DPIs, respectively. The inhalation flow against time was recorded to provide the peak inhalation flow (PIF; in L/min), the maximum pressure change (DP; in kPa), acceleration rates (ACCEL; in kPa/sec), time to maximum inhalation, the length of each inhalation (in sec), and the inhalation volume (IV; in liters) of each inhalation maneuver. Results: PIF, DP, and ACCEL values were consistent with the order of the inhaler's resistance. For each device, the inhalation characteristics were in the order ADULT > COPD > CHILD for PIF, DP, and ACCEL ( p < 0.001). The results showed a large variability in inhalation characteristics and demonstrate the advantages of DP and ACCEL rather than PIFs. Overall inhaled volumes were low, and only one patient achieved an IV > 4 L and DP > 4 kPa. Conclusion: The large variability of these inhalation characteristics and their range highlights that if inhalation profiles were used with compendial in vitro dose emission measurements, then the results would provide useful information about the dose patients inhale during routine use. The inhalation characteristics highlight that adults with asthma have greater inspiratory capacity than patients with COPD, whereas children with asthma have the lowest. The significance of the inhaled volume to empty doses from each device requires investigation.

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Section: Dry Powder Inhaler Inhalation Maneuversmentioning

confidence: 96%

The Inhalation Characteristics of Patients When They Use Different Dry Powder Inhalers

Azouz

Chetcuti

Hosker

et al. 2015

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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“…The baseline model was coupled with the inhaler of the medication the patient previously used (i.e., Oxis Turbuhaler; MMAD = 2.64; GSD = 1.91)) (20) and with the Foster inhaler. Two CFD-based deposition analysis were performed using the methodology described and validated in De Backer et al, (7) one with the original inhaler and the corresponding formulation and one with the Foster inhaler with the extrafine particle formulation.…”

Section: Cfd Based Deposition Analysismentioning

confidence: 99%

The Effects of Extrafine Beclometasone/Formoterol (BDP/F) on Lung Function, Dyspnea, Hyperinflation, and Airway Geometry in COPD Patients: Novel Insight Using Functional Respiratory Imaging

Backer

Vos²,

Vinchurkar³

et al. 2015

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: The efficacy of inhaled corticosteroids (ICS) in moderately severe COPD patients remains unclear. At the same time, the use of extrafine particles in COPD patients is a topic of ongoing research. Objectives: This study assessed the effect of ICS in steroid-naïve mild COPD patients and the effect of reducing the ICS dose in more severe COPD patients previously using ICS when switching to an extrafine particle BDP/F formulation (Foster using Modulite technology, Chiesi Pharmaceutici, Parma, Italy). Methods: Novel functional respiratory imaging (FRI) methods, consisting of multi-slice CT scans and Computational Fluid Dynamics, were used in combination with conventional pulmonary function tests and patient reported outcomes. Results: The study showed that the administration of extrafine BDP/F after 4-6 h led to a significant improvement in lung function parameters and hyperinflation as determined by spirometry, body plethysmography, and functional respiratory imaging. After 6 months of treatment, it was observed that, compared to baseline, the hyperinflation on lobar level at total lung capacity was significantly reduced (-1.19 -7.19 %p, p¼0.009). In addition, a significant improvement in SGRQ symptom score was noted in the entire patient population. Patients who improved in terms of hyperinflation also improved their MMRC dyspnea score. CFD indicated a difference in regional deposition between extrafine and non-extrafine formulations with -11% extrathoracic deposition and up to + 4% lobe deposition for the extrafine formulation. Conclusions: The study showed that the administration of extrafine BDP/F improved lung function parameters and hyperinflation. Patients previously treated with ICS remained stable despite the lower dose, while ICS naïve patients improved in terms of lobar hyperinflation. FRI seems to be a sensitive biomarker to detect clinically relevant changes that are not detected by spirometry. The next step is to confirm these findings in a controlled trial.

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“…The problem of L-R inhalers is that they are typically flowdependent, i.e. the mass and particle size distribution of the aerosol they release are significantly improved when flow increases (Weuthen T. et al, 2002;Azouz W. et al, 2015). Powder de-agglomeration is better at high airflow rates but at the same time the aerosol velocity at the inlet to the mouth becomes higher, which increases undesired drug deposition in the oro-pharynx.…”

Section: Inhaler Design and Performancementioning

confidence: 99%

Powder Particles and Technologies for Medicine Delivery to the Respiratory System: Challenges and Opportunities

Sosnowski¹

2018

KONA

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The paper discusses essential engineering challenges related to the application of powder medicines for pulmonary delivery as inhaled aerosol. Starting from a physically based description of the complexity of aerosol dynamics inside the respiratory system, the paper discusses several technical factors responsible for efficient drug delivery to the lungs: (i) interparticle interactions-which can be tuned by selection and control of powder manufacturing methods, (ii) inhaler design-as a determinant of flow dynamics through the inhaling device and degree of powder dispersion, (iii) the dynamics of inhalation in a given inhaler-which is related to patient-device interaction. Basic information on the standard (compendial) methods of the quantitative evaluation of dry powder inhalers (DPIs) are presented with a special focus on the correct data interpretation and the consequences for in vivo-in vitro correlation (IVIVC) problems. Some issues regarding the development of inhalation products (including generics) are also briefly highlighted. Finally, possible strategies of powder particle functionalization to obtain the required bioavailability are outlined on the basis of knowledge on the physicochemical interactions of inhaled particles with the lung fluids.

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In Vitro Testing of Two Formoterol Dry Powder Inhalers at Different Flow Rates

Cited by 44 publications

References 16 publications

The Inhalation Characteristics of Patients When They Use Different Dry Powder Inhalers

The Inhalation Characteristics of Patients When They Use Different Dry Powder Inhalers

The Effects of Extrafine Beclometasone/Formoterol (BDP/F) on Lung Function, Dyspnea, Hyperinflation, and Airway Geometry in COPD Patients: Novel Insight Using Functional Respiratory Imaging

Powder Particles and Technologies for Medicine Delivery to the Respiratory System: Challenges and Opportunities

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