An Investigation into the Powder Release Behavior from Capsule-Based Dry Powder Inhalers

Huynh, Bao K.; Chen, Y.; Fletcher, David F.; Young, Paul M.; Zhu, Bing; Traini, Daniela

doi:10.1080/02786826.2015.1082532

Cited by 12 publications

(7 citation statements)

References 20 publications

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“…The aerosol performance of TPIP in the RS01 devices compares favorably to published data for other micronized and spray-dried powders. Huynh et al (2015) evaluated 20 mg micronized mannitol (median size of 5 µm) in the LR and HR devices. The ED for micronized mannitol was 73.8 and 72.5%, respectively, lower than that observed for all capsule doses of TPIP.…”

Section: Discussionmentioning

confidence: 99%

“…There are multiple RS01 device designs with varying resistances to airflow, and for the same inspiratory effort, the air flow rate will decrease as the device resistance increases. This enables the drug developer to select the device that most effectively disperses their powder formulation at an inspiratory effort that can be effectively achieved by their patient population (Huynh et al, 2015;Sahay et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation and Selection of the Inhaler Device for Treprostinil Palmitil Inhalation Powder

Gauani

Baker

et al. 2022

Front. Drug Deliv.

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Treprostinil palmitil (TP) is a prodrug of treprostinil that has been formulated as an inhaled powder, termed TPIP, for evaluation in patients with pulmonary arterial hypertension. In these characterization studies we investigated the aerosol performance of TPIP in response to changes in capsule fill, device resistance, and inspiratory flow rate to enable selection of an inhaler for clinical use. Capsules containing 8, 16 or 32 mg of TPIP (80, 160, or 320 μg TP, respectively) were evaluated using four commercially-available, breath-actuated RS01 devices (Plastiape, S. p.A., Osnago, Italy) with low, medium, high or ultra-high inspiratory resistances, creating 12 different capsule and device configurations for evaluation. Aerosol characterization was performed using the next generation impactor at compendial conditions of 23°C and 35% relative humidity and a flow rate corresponding to a 4 kPa pressure drop. The aerosol mass median aerodynamic diameter, geometric standard deviation, fine particle fraction, emitted dose and fine particle dose (FPD) were calculated from the in vitro impactor data. The TP emitted dose at 4 kPa exceeded 75% for all 12 capsule and device configurations. The FPD, an estimate of the respirable dose, varied between 61.0 and 70.6% of the loaded TP dose for all four devices with the 8 and 16 mg TPIP capsule dose. For the 32 mg TPIP capsule dose, the FPD remained above 61.0% for the high and ultra-high resistance devices but decreased to 48.5 and 52.6% for the low and medium resistance devices, respectively. Based on this initial data, the high resistance device was selected for additional characterization studies at 40 and 80 L/min corresponding to pressure drops of 1.4 and 5.4 kPa. The FPD was relatively insensitive to changes in flow rate, providing an expectation of a consistent total lung dose of TP under scenarios simulating variability in how the device is used. Based on these findings, the high resistance device was chosen for further development in human clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation and Selection of the Inhaler Device for Treprostinil Palmitil Inhalation Powder

Gauani

Baker

et al. 2022

Front. Drug Deliv.

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“…Coates et al also demonstrated that reducing the inlet size of Aerolizer TM from full to one third also increased the axial velocity of the capsule, increased the capsule emptying rate and the amount of powder being emitted before full flow development, leading to 8% reduction in the FPF of mannitol. Huynh et al confirmed using laser obscuration (Spraytech) that the rate of powder emission from the capsule of the high resistance Osmohaler TM (smaller air inlet size) was marginally greater than the low resistance Osmohaler (larger air inlet size) (Huynh et al, 2015). This may help to explain the small 4% difference in FPF between the high (26% FPF) and low resistance (30% FPF) Osmohaler TM .…”

Section: Discussionmentioning

confidence: 87%

“…The observed flow dependency of particle size on the dispersion flow rates up to 120 L/min (for low resistance Osmohaler TM ) can be explained by Coates et al who reported that at higher dispersion flow rate of 120 L/min, a greater amount of powder can be emptied from the capsule before the full flow development (Coates et al, 2005;Huynh et al, 2015). This means less fraction of the emitted aerosol is de-agglomerated by the optimum turbulence and device-impaction energy level, leading to a less efficient powder deagglomeration and larger particle size distribution of the aerosol.…”

Section: Discussionmentioning

confidence: 88%

The effect of device resistance and inhalation flow rate on the lung deposition of orally inhaled mannitol dry powder

Yang

Verschuer

Shi

et al. 2016

International Journal of Pharmaceutics

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The present study investigates the effect of DPI resistance and inhalation flow rates on the lung deposition of orally inhaled mannitol dry powder. Mannitol powder radiolabeled with Tc-DTPA was inhaled from an Osmohaler™ by healthy human volunteers at 50-70L/min peak inhalation flow rate (PIFR) using both a low and high resistance Osmohaler™, and 110-130L/min PIFR using the low resistance Osmohaler™ (n=9). At 50-70L/min PIFR, the resistance of the Osmohaler™ did not significantly affect the total and peripheral lung deposition of inhaled mannitol [for low resistance Osmohaler™, 20% total lung deposition (TLD), 0.3 penetration index (PI); for high resistance Osmohaler™, 17% TLD, 0.23 PI]. Increasing the PIFR 50-70L/min to 110-130L/min (low resistance Osmohaler™) significantly reduced the total lung deposition (10% TLD) and the peripheral lung deposition (PI 0.21). The total lung deposition showed dependency on the in vitro FPF (R=1.0). On the other hand, the PI had a stronger association with the MMAD (R=1.0) than the FPF (R=0.7). In conclusion the resistance of Osmohaler™ did not significantly affect the total and regional lung deposition at 50-70L/min PIFR. Instead, the total and regional lung depositions are dependent on the particle size of the aerosol and inhalation flow rate, the latter itself affecting the particle size distribution.

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“…Relevant studies are still scarce in the literature, due to the complexity of the problem that includes the motion, physical state and emptying behaviour of capsule, as stated by Huynh et al [ 73 ]. Several issues have been identified, which may potentially affect their predicting capabilities of the available models.…”

Section: Review Of Up-to-date Dpi Modelling Studiesmentioning

confidence: 99%

Flow and Particle Modelling of Dry Powder Inhalers: Methodologies, Recent Development and Emerging Applications

2021

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Dry powder inhaler (DPI) is a device used to deliver a drug in dry powder form to the lungs. A wide range of DPI products is currently available, with the choice of DPI device largely depending on the dose, dosing frequency and powder properties of formulations. Computational fluid dynamics (CFD), together with various particle motion modelling tools, such as discrete particle methods (DPM) and discrete element methods (DEM), have been increasingly used to optimise DPI design by revealing the details of flow patterns, particle trajectories, de-agglomerations and depositions within the device and the delivery paths. This review article focuses on the development of the modelling methodologies of flow and particle behaviours in DPI devices and their applications to device design in several emerging fields. Various modelling methods, including the most recent multi-scale approaches, are covered and the latest simulation studies of different devices are summarised and critically assessed. The potential and effectiveness of the modelling tools in optimising designs of emerging DPI devices are specifically discussed, such as those with the features of high-dose, pediatric patient compatibility and independency of patients’ inhalation manoeuvres. Lastly, we summarise the challenges that remain to be addressed in DPI-related fluid and particle modelling and provide our thoughts on future research direction in this field.

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An Investigation into the Powder Release Behavior from Capsule-Based Dry Powder Inhalers

Cited by 12 publications

References 20 publications

Evaluation and Selection of the Inhaler Device for Treprostinil Palmitil Inhalation Powder

Evaluation and Selection of the Inhaler Device for Treprostinil Palmitil Inhalation Powder

The effect of device resistance and inhalation flow rate on the lung deposition of orally inhaled mannitol dry powder

Flow and Particle Modelling of Dry Powder Inhalers: Methodologies, Recent Development and Emerging Applications

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