Lactose Composite Carriers for Respiratory Delivery

Young, Paul M.; Kwok, Philip Chi Lip; Adi, Handoko; Chan, Hak‐Kim; Traini, Daniela

doi:10.1007/s11095-008-9779-9

Cited by 50 publications

(32 citation statements)

References 31 publications

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“…Both properties affect the adhesive interactions and therefore the performance of the formulation. 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).…”

Section: Topographical Imagingmentioning

confidence: 99%

“…Researchers rely on the root mean square (RMS) roughness (Berard et al, 2002a,b;Bouhroum et al, 2010;Hickey et al, 2007;Hooton et al, 2006a,b;Traini et al, 2006;Young et al, 2009), and sometimes also include the arithmetic average (Begat et al, 2004a;Kinnunen et al, 2014).…”

Section: Topographical Imagingmentioning

confidence: 99%

“…3) to evaluate both the cohesive and adhesive interactions between materials used in drug delivery (Adi et al, 2007;Beilmann et al, 2007;De Boer et al, 2003a,b;Eve et al, 2002;James et al, 2008;Karner et al, 2014;Louey et al, 2001;Price et al, 2002;Sindel and Zimmermann, 2001;Tsukada et al, 2004;Young et al, 2009) and, quite recently, the mechanism of particle detachment (Cui and Sommerfeld, 2015). While three different scenarios describing the process of particle detachment-lift-off, sliding and rolling-are possible, a combination of colloidal probe measurements, simulations and computational modelling identified the rolling mechanism, closely followed by sliding, as the main mechanisms of particle detachment.…”

Section: Adhesion Measurementsmentioning

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: Topographical Imagingmentioning

confidence: 99%

Section: Topographical Imagingmentioning

confidence: 99%

Section: Adhesion Measurementsmentioning

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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“…The surface morphology and physicochemical properties of the composite carriers were considerably different from regular α-lactose monohydrate.In all cases the composite carriers resulted in improved drug aerosol performance. It was suggested that composite based carriers are a potential route to control drug-carrier adhesion forces and variability thus allowing more precise control of formulation performance (Young et al, 2009 ).…”

Section: Composite Lactosementioning

confidence: 99%

The Role of Carrier in Dry Powder Inhaler

Hamishehkar¹,

Rahimpour²,

Javadzadeh³

2012

Recent Advances in Novel Drug Carrier Systems

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“…To solve these problems, it is usual for an excipient, such as coarse lactose monohydrate, to be formulated to physically attach to fine active ingredients. 8,9) It has been recently reported that the addition of amino acids or cyclodextrins (CyDs) as excipients improves pulmonary delivery. 10,11) As for fundamental research on DPIs, evaluation of the physical properties such as particle size and pulmonary deposition is mainstream, whereas biological evaluation such as of the efficacy and safety is essential for clinical application.…”

mentioning

confidence: 99%

Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air–Liquid Interface Cultured Cell Layer

Asai

Okuda

Yamauchi

et al. 2016

Biological & Pharmaceutical Bulletin

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Most safety evaluations of dry powder inhalers (DPIs) using cultured cells have been performed with dry powder formulations dissolved in a medium. However, this method is not considered to be suitable to evaluate the safety of inhaled dry powder formulations correctly since it cannot reflect the actual phenomenon on the respiratory epithelial surface. In this study, we established a novel in-vitro safety evaluation system suitable for DPIs by combining an air-liquid interface cultured cell layer and a device for dispersing dry powders, and evaluated the safety of candidate excipients of dry powders for inhalation. The safety of excipients (sugars, amino acids, cyclodextrins, and positive controls) in solutions was compared using submerged cell culture systems with a conventional 96-well plate and Transwell ® . The sensitivity of the cells grown in Transwell ® was lower than that of those grown in the 96-well plate. Dry powders were prepared by spray-drying and we evaluated their safety with a novel in-vitro safety evaluation system using an air-liquid interface cultured cell layer. Dry powders decreased the cell viability with doses more than solutions. On the other hand, dissolving the dry powders attenuated their cytotoxicity. This suggested that the novel in-vitro safety evaluation system would be suitable to evaluate the safety of DPIs with high sensitivity.Key words dry powder; safety evaluation; air-liquid interfaced culture; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; A549 cell Pulmonary drug delivery has been investigated as not only a local treatment for respiratory diseases such as asthma or chronic obstructive pulmonary disease, but also as an alternative route for the systemic delivery of macromolecule drugs such as insulin, calcitonin, and heparin. 1-4)Among the three major systems for pulmonary deliverynebulizers, pressurized metered-dose inhalers (pMDIs), and dry powder inhalers (DPIs)-DPIs have several advantages, including favorable portability, a low cost, and the lack of a need for propellants. Furthermore, the handling of DPIs is easier than that of pMDIs because of breath-actuated passive aerosolization. 5)For effective pulmonary deposition after inhalation, in general, the optimal aerodynamic diameter of drug particles is less than 6 µm.6,7) However, micronized drug particles tend to be highly cohesive and poorly flowable, leading to low-level performance. To solve these problems, it is usual for an excipient, such as coarse lactose monohydrate, to be formulated to physically attach to fine active ingredients. 8,9) It has been recently reported that the addition of amino acids or cyclodextrins (CyDs) as excipients improves pulmonary delivery. 10,11) As for fundamental research on DPIs, evaluation of the physical properties such as particle size and pulmonary deposition is mainstream, whereas biological evaluation such as of the efficacy and safety is essential for clinical application. 12)These biological evaluations of dry powder formulations are often conduct...

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Lactose Composite Carriers for Respiratory Delivery

Abstract: Composite based carriers are a potential route to control drug-carrier adhesion forces and variability thus allowing more precise control of formulation performance.

Cited by 50 publications

References 31 publications

Characterisation of dry powder inhaler formulations using atomic force microscopy

Characterisation of dry powder inhaler formulations using atomic force microscopy

The Role of Carrier in Dry Powder Inhaler

Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air–Liquid Interface Cultured Cell Layer

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