Influence of size and surface roughness of large lactose carrier particles in dry powder inhaler formulations

Donovan, Martín J.

doi:10.1016/j.ijpharm.2010.08.045

Cited by 103 publications

(82 citation statements)

References 26 publications

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“…The in vitro performance of DPIs depends significantly on the formulation and device properties. The physicochemical properties of drug substance and drug carrier (lactose), such as particle size, shape, density, surface area, roughness, and morphology (4)(5)(6)(7)(8)(9), have been shown to affect particle interactions, stability, ease of dispersion, and deaggregation. The internal geometry of a DPI device (e.g., the dimensions and shape of the air channels) is known to play an important role in determining the device resistance.…”

Section: Introductionmentioning

confidence: 99%

Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers

Adams¹,

Lee

Plourde

et al. 2012

AAPS J

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Abstract. The study examined the sensitivity of DPI in vitro performance to formulation and device changes. Rotahaler/Rotacaps was selected as the reference DPI drug product, and Aerolizer was selected as the test device. Since the test device was recognized to have much greater efficiency of dispersion, simple modifications to both formulation and device were made in an effort to provide a closer match to the in vitro performance of the reference product. The modifications included varying the drug and lactose particle sizes and/or lactose fine particle content in the test formulations, as well as lowering the specific resistance of the test device. These modifications were intended to address variables important for drug product performance for a defined experimental design and were not intended to mimic the extensive formulation and device design strategies that are employed in an industrial setting. Formulation and device modifications resulted in a modified test product that approached the reference product in the in vitro performance.

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Section: Introductionmentioning

confidence: 99%

Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers

Adams¹,

Lee

Plourde

et al. 2012

AAPS J

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“…Ooi et al (2011) concluded that the adhesive forces between model polystyrene carrier particles and micronised salbutamol sulphate particles were unaffected by the diameter of the carrier particles. In contrast, results published by Donovan and Smyth (2010) suggested that the impact of increased carrier size on aerosolisation performance strongly depends on the roughness of the excipient. Larger carrier particles with rougher surfaces enhanced the dispersion performance of a budesonide-lactose blend while the size of smooth lactose particles had to be reduced to improve the dispersibility.…”

Section: Adhesion Measurementsmentioning

confidence: 78%

“…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). The relationship between particulate characteristics and their respective effects on formulation performance have been studied and reviewed widely over the years (Adi et al, 2013;Chan, 2008;Chow et al, 2007;Donovan and Smyth, 2010;Guenette et al, 2009;Healy et al, 2014;Zellnitz et al, 2014;Zeng et al, 2000;Zhang et al, 2011).…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

“…Particle surface roughness (Donovan and Smyth, 2010;Hooton et al, 2006a;Kaialy and Nokhodchi, 2013b) Degradation during storage or processing (Begat et al, 2003) Crystal growth (Durbin and Carlson, 1992;Price and Young, 2004) Crystallinity (Begat et al, 2003;Ward et al, 2005) Polymorphism (Danesh et al, 2000;Hooton et al, 2006a) 3D imaging of the particle (Hooton et al, 2006a) Nanoindentation Elastic modulus (local)…”

Section: Phase Imagingmentioning

confidence: 99%

“…Numerous groups (Bosquillon et al, 2001;Donovan and Smyth, 2010;Flament et al, 2004;Heng et al, 2000;Jones and Price, 2006;Kinnunen et al, 2014;Ooi et al, 2011;Young et al, 2009;Zellnitz et al, 2013Zellnitz et al, , 2014 investigated the correlation between excipient particle size, surface roughness and formulation performance with the aim of optimising these properties. Formulation performance was related to particle size and roughness of a budesonide-lactose formulation by Donovan and Smyth (2010); particle roughness and adhesion of a terbutaline sulphate-lactose formulation by Flament et al (2004); and to the percentage of carrier surface coverage in a model salbutamol sulphate formulation by Zellnitz et al (2014). Ferrari et al (2004) looked at the effect of wet-smoothing on the rugosity of lactose carrier particles.…”

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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Particle Surface Roughness – Its Characterisation and Impact on Dry Powder Inhaler Performance

Tan

Liew

Chan

et al. 2015

Pulmonary Drug Delivery

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Influence of size and surface roughness of large lactose carrier particles in dry powder inhaler formulations

Cited by 103 publications

References 26 publications

Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers

Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers

Characterisation of dry powder inhaler formulations using atomic force microscopy

Particle Surface Roughness – Its Characterisation and Impact on Dry Powder Inhaler Performance

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