In vitro evaluation of dry powder inhalers II: influence of carrier particle size and concentration on in vitro deposition

Steckel, Hartwig; Müller, Bernd W.

doi:10.1016/s0378-5173(97)00115-4

Cited by 119 publications

(58 citation statements)

References 13 publications

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“…As a part of DPI formulation investigation, carrier property has been studied in various ways. 9) And various factors have been reported to affect the inhalation property of DPI formulations, for example, humidity, 10,11) air flow, 12) inhaler design, 4,13) particle size 14) and carrier surface property. 6,7,15) Among these properties, carrier surface property would be considered preferable to apply pharmaceutical ideas to improve the inhalation property.…”

mentioning

confidence: 99%

Novel Approach to DPI Carrier Lactose with Mechanofusion Process with Additives and Evaluation by IGC

et al. 2006

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confidence: 99%

Novel Approach to DPI Carrier Lactose with Mechanofusion Process with Additives and Evaluation by IGC

et al. 2006

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“…The particle size, size distribution (4), morphology, surface roughness (5), surface area, flowability (6), and surface energy (7) of lactose carriers all have been shown to have an influence on the DPI formulation performance. Amongst, the size and roughness of lactose carriers have been extensively investigated (2,4,(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

“…As a result of these research findings, it was widely believed that carrier particles with smaller diameters were preferable to maximize aerosolization efficiency, with the consensus that increasing diameters and surface roughness hinder efficient drug dispersion performance (4,14,(16)(17)(18)(19)(20). However, it was found recently that lactose carriers with large size fraction can also improve aerosol performance, especially when combined with significantly rough surface (13).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Granulated Lactose as a Carrier for DPI Formulations 1: Effect of Granule Size

2014

AAPS PharmSciTech

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ABSTRACT. The objective of this study was to investigate the effect of large granulated lactose carrier particle systems on aerosol performance of dry powder inhaler formulations. Granulated lactose carriers with average sizes ranging from 200 to 1,000 μm were prepared and subsequently fractionated into separate narrow size powders. The fractionated granulated lactose (GL) samples were characterized in terms of size, specific surface area, surface roughness, morphology, density, flowability, and solid-state. The in vitro aerosolization performance was performed on the different size fractions of GL samples from a commercial inhaler device (Aerolizer®) with a model formulation (2% w/w salbutamol sulfate). The cascade impaction parameters employed were 60 or 90 L/min with standard (aperture size, 0.6 mm) or modified piercing holes (aperture size, 1.2 mm) of the inhaler loaded capsules. It was shown that the largest size fraction formulation (850-1000 μm) had a slight improvement in the fine particle fraction (FPF) compared to immediately preceding size fractions, explained by a smaller adhesive force between drug and carrier. Compared to commercial piercing holes, enlarged piercing holes generated a slight decreasing trend of FPF as the lactose powder sizes increased from 200-250 μm to 600-850 μm, perhaps due to the reduced detachment force by flow forces. The size, surface roughness, density, and flowability of lactose carrier as well as device design all contributed to the aerosol dispersion performance of granulated lactose-based adhesive mixtures. It was concluded that poorer or enhanced redispersion performance is not an inherent property to the significantly large size of granulated lactose carriers as previously contended.

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“…The particle-particle interaction forces have to be sufficiently strong that fine API particles can adhere with the carriers or form large agglomerates to be transported, but weak enough that they can be detached or dispersed by a deagglomeration process and thus allow the delivery of the API particles into the respiratory tracts and lungs. Therefore, particle-particle interactions play a significant role in controlling the performance of DPIs and hence many studies have been performed to explore the dependency of these interactions on particle size [7,8], material properties [9,10], particle concentration [11,12], particle morphology [13,14], particle surface roughness [15,16], storage conditions [17,18], surface area [19], density and porosity [20], and crystal form [21]. For example, Kaialy et al [7] experimentally examined the influence of the particle size of lactose carrier on the DPI performance and demonstrated that the DPI performance improved with decreasing carrier particle size.…”

Section: Introductionmentioning

confidence: 99%

DEM analysis of particle adhesion during powder mixing for dry powder inhaler formulation development

Yang

Adams

2013

Granular Matter

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Understanding the adhesive interactions between active pharmaceutical ingredient (API) particles and carrier particles in dry powder inhalers (DPIs) is critical for the development of formulations and process design. In the current study, a discrete element method (DEM), which accounts for particle adhesion, is employed to investigate the attachment processes in DPIs. A critical velocity criterion is proposed to determine the lowest impact velocity at which two elastic autoadhesive spherical particles will rebound from each other during impact. Furthermore, the process of fine API particles adhering to a large carrier in a vibrating container is investigated. It was found that there is an optimal amplitude and frequency for the vibration velocity that can maximise the number of particles contacting with the carrier (i.e. the contact number). The impact number and detachment number during the vibration process both increase with increasing vibration amplitude and frequency while the sticking efficiency decreases as the amplitude and frequency is increased.

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In vitro evaluation of dry powder inhalers II: influence of carrier particle size and concentration on in vitro deposition

Cited by 119 publications

References 13 publications

Novel Approach to DPI Carrier Lactose with Mechanofusion Process with Additives and Evaluation by IGC

Novel Approach to DPI Carrier Lactose with Mechanofusion Process with Additives and Evaluation by IGC

Evaluation of Granulated Lactose as a Carrier for DPI Formulations 1: Effect of Granule Size

DEM analysis of particle adhesion during powder mixing for dry powder inhaler formulation development

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