Towards the optimisation and adaptation of dry powder inhalers

Cui, Yan; Schmalfuß, Silvio; Zellnitz, Sarah; Sommerfeld, Martin; Urbanetz, Nora Anne

doi:10.1016/j.ijpharm.2014.04.065

Cited by 44 publications

(30 citation statements)

References 19 publications

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“…In order to reach the targeted sites in the respiratory tract, the API needs to penetrate the deep lung (Cui et al, 2014). Upon inhalation, the drug particles are subject to different deposition mechanisms-impaction, sedimentation and diffusion-depending on their size (Heyder, 2004;Zeng et al, 2000).…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

“…For optimum efficacy, the particles' aerodynamic diameters should be between 1 mm and 5 mm (Cui et al, 2014). However, other particle and formulation characteristics are critical too.…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

“…If excipients are included in the formulation, carrier particle size and texture also have to be considered. The forces acting both between drug particles and between drug and excipient particles are of high importance: they have to be strong enough to allow for easy formulation preparation and to prevent segregation during transport and storage (Cui et al, 2014). At the same time, they need to be low enough to ensure dispersion and disaggregation during inhalation (Cui et al, 2014), as only small particles and agglomerates (<5 mm) can penetrate the deep lung and be therapeutically active (Cui et al, 2014;Zeng et al, 2000).…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

“…The forces acting both between drug particles and between drug and excipient particles are of high importance: they have to be strong enough to allow for easy formulation preparation and to prevent segregation during transport and storage (Cui et al, 2014). At the same time, they need to be low enough to ensure dispersion and disaggregation during inhalation (Cui et al, 2014), as only small particles and agglomerates (<5 mm) can penetrate the deep lung and be therapeutically active (Cui et al, 2014;Zeng et al, 2000). The drug load itself also affects formulation performance along with the choice of inhaler device (De Boer et al, 2005) and the patient's individual breathing pattern (Chrystyn and Price, 2009;Heyder, 2004).…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

“…Compared to commercial and spray-dried mannitol, the freeze-dried particles (Kaialy and Nokhodchi, 2013a) showed a lower roughness which might account for the improved aerosolisation performance (Kaialy and Nokhodchi, 2013a;Zeng et al, 2000). At the same time, the fine particle fraction (FPF) (the fraction of particles in the emitted dose with D ae 5 mm (Cui et al, 2014)) was comparatively high. Similarly, the treatment of mannitol particles in a saturated mannitol solution also decreased surface roughness and yielded high FPFs (Kaialy and Nokhodchi, 2013b).…”

Section: Topographical Imagingmentioning

confidence: 99%

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Characterisation of dry powder inhaler formulations using atomic force microscopy

Weiss

McLoughlin

Cathcart

2015

International Journal of Pharmaceutics

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A B S T R A C TInhalation formulations are a popular way of treating the symptoms of respiratory diseases. The active pharmaceutical ingredient (API) is delivered directly to the site of action within the deep lung using an inhalation device such as the dry powder inhaler (DPI).The performance of the formulation and the efficiency of the treatment depend on a number of factors including the forces acting between the components. In DPI formulations these forces are dominated by interparticulate interactions. Research has shown that adhesive and cohesive forces depend on a number of particulate properties such as size, surface roughness, crystallinity, surface energetics and combinations of these. With traditional methods the impact of particulate properties on interparticulate forces could be evaluated by examining the bulk properties. Atomic force microscopy (AFM), however, enables the determination of local surface characteristics and the direct measurement of interparticulate forces using the colloidal probe technique. AFM is considered extremely useful for evaluating the surface topography of a substrate (an API or carrier particle) and even allows the identification of crystal faces, defects and polymorphs from high-resolution images. Additionally, information is given about local mechanical properties of the particles and changes in surface composition and energetics. The assessment of attractive forces between two bodies is possible by using colloidal probe AFM.This review article summarises the application of AFM in DPI formulations while specifically focussing on the colloidal probe technique and the evaluation of interparticulate forces.2015 Elsevier B.V. All rights reserved.

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Section: Pulmonary Drug Deliverymentioning

confidence: 99%

“…For optimum efficacy, the particles' aerodynamic diameters should be between 1 mm and 5 mm (Cui et al, 2014). However, other particle and formulation characteristics are critical too.…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

Section: Topographical Imagingmentioning

confidence: 99%

See 3 more Smart Citations

Characterisation of dry powder inhaler formulations using atomic force microscopy

Weiss

McLoughlin

Cathcart

2015

International Journal of Pharmaceutics

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Computational Modeling of Dry Powder Inhalation

Hu,

Zhang,

2024

Exploring Computational Pharmaceutics ‐ AI and Modeling in Pharma 4.0

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Simulation of dry powder inhalers: Combining micro‐scale, meso‐scale and macro‐scale modeling

et al. 2016

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The flow of carrier particles, coated with active drug particles, is studied in a prototype dry powder inhaler. A novel, multiscale approach consisting of a discrete element model (DEM) to describe the particles coupled with a dynamic large eddy simulation (LES) model to describe the dynamic nature of the flow is applied. The model consists of three different scales: the micro‐scale, the meso‐scale, and the macro‐scale. At the micro‐scale, the interactions of the small active drug particles with larger carrier particles, with the wall, with the air flow, and with each other is thoroughly studied using discrete element modeling and detailed computational fluid dynamics (CFD), i.e., resolving the flow structures around the particles. This has led to the development of coarse‐grained models, describing the interaction of the small active drug particles at the larger scales. At the meso‐scale the larger carrier particles, and all of their interactions are modeled individually using DEM and CFD‐LES. Collisions are modeled using a visco‐elastic model to describe the local deformation at each point of particle‐particle contact in conjunction with a model to account for cohesion. At the macro‐scale, simulations of a complete prototype inhaler are carried out. By combining the relevant information of each of the scales, simulations of the inhalation of one dose from a prototype inhaler using a patient relevant air flow profile show that fines leave the inhaler faster than the carrier particles. The results also show that collisions are not important for particle‐particle momentum exchange initially but become more important as the particles accelerate. It is shown that for the studied prototype inhaler the total release efficiency of the fine particles is between 10 and 30%, depending on the Hamaker constant, using typical settings for the properties of both particles. The results are also used to study regions of recirculation, where carrier particles can become trapped, and regions where fines adhere to the wall of the device. © 2016 American Institute of Chemical Engineers AIChE J, 63: 501–516, 2017

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Towards the optimisation and adaptation of dry powder inhalers

Cited by 44 publications

References 19 publications

Characterisation of dry powder inhaler formulations using atomic force microscopy

Characterisation of dry powder inhaler formulations using atomic force microscopy

Computational Modeling of Dry Powder Inhalation

Simulation of dry powder inhalers: Combining micro‐scale, meso‐scale and macro‐scale modeling

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