The interaction between carrier rugosity and carrier payload, and its effect on drug particle redispersion from adhesive mixtures during inhalation

Dickhoff, Bastiaan H.J.; Boer, de Anne; Lambregts, Dorette; Frijlink, Henderik W.

doi:10.1016/j.ejpb.2004.07.005

Cited by 41 publications

(21 citation statements)

References 21 publications

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“…The surface roughness on both sides of the film varied between 85 ± 20 nm, indicating a smooth surface relative to the size of the drug particle size scale. Hence we expect that these surface irregularities of the film are not sufficient enough to shield the drug particles from experiencing the press-on forces during mixing as it was seen with coarse lactose particles (Smyth and Hickey 2005;Lida et al 2000a;Podczeck 1998b;Zeng et al 2000;Dickhoff et al 2005). …”

Section: Resultsmentioning

confidence: 99%

Micronized Drug Adhesion and Detachment from Surfaces: Effect of Loading Conditions

Selvam

Marek

Truman

et al. 2011

Aerosol Science and Technology

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Drug loading and processing conditions in a dry powder inhaler system are critical for performance of the system since it is these forces that must be overcome to properly redisperse respirable particles. In this work, we have investigated the effects of different loading forces for adhering micronized drug onto surfaces on the drug adhesion, detachment, and aerosol performance under controlled conditions. Drug loading onto a standardized surface was performed under three different loading conditions using turbulamixer to actively induce powder-surface interactions. It was seen the drug loading increased with increased processing time. The presence of external press-on force also increased drug loading. Drug detachment studies performed using centrifugation method indicated that adhesion forces were the lowest at lower mixing time and increased with increasing press-on forces. Drug aerosolization performance from the surface was assessed using a prototype DPI and confirmed that external forces during drug loading and coating processing played an important role in drug dispersion. It was seen that the respirability of drug particles correlated with mixing times as well as the press-on forces.

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Section: Resultsmentioning

confidence: 99%

Micronized Drug Adhesion and Detachment from Surfaces: Effect of Loading Conditions

Selvam

Marek

Truman

et al. 2011

Aerosol Science and Technology

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“…During powder mixing, frictional and inertial press on are related to the adhesion of drug particles on the carrier surface (14). The differences of these forces in the different lactose size fractions may explain the improvement of aerosol redispersion observed with the coarsest fraction of granulated lactose.…”

Section: Adhesion Forces and Bulk Powder Propertiesmentioning

confidence: 99%

“…Since the surface roughness of granulated lactose increased with increasing size fractions (Fig. 6b), the larger lactose could be expected to provide a larger volume of surface pores to shelter a significantly higher amount of drugs from press on forces during mixing (14). As a result, larger granulated lactose particles could be potential carriers for high drug loading dry powder inhalation formulations.…”

Section: Adhesion Forces and Bulk Powder Propertiesmentioning

confidence: 99%

“…Additionally, larger lactose particles may exhibit higher press-on forces (defined as the adhesive forces between drug and carrier particles) (14) during mixing with the micronized API due to larger mass and inertia force, resulting in a stronger adhesive force between drug and lactose carrier (15). Also, as the size of lactose carrier is increased, the amount of fine lactose (<32 μm) present in the powder tends to decrease (16).…”

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%

See 2 more Smart Citations

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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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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The interaction between carrier rugosity and carrier payload, and its effect on drug particle redispersion from adhesive mixtures during inhalation

Cited by 41 publications

References 21 publications

Micronized Drug Adhesion and Detachment from Surfaces: Effect of Loading Conditions

Micronized Drug Adhesion and Detachment from Surfaces: Effect of Loading Conditions

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

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

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