Effect of particle morphology on the triboelectrification in dry powder inhalers

Murtomaa, Matti; Mellin, Velipekka; Harjunen, Päivi; Lankinen, Tapio; Laine, E.; Lehto, Vesa‐Pekka

doi:10.1016/j.ijpharm.2004.06.002

Cited by 72 publications

(41 citation statements)

References 19 publications

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“…Furthermore, the addition of a fine-lactose excipient ( 10 μm) to coarse lactose decreases the magnitude of triboelectrification during mixing [25]. The increase in amorphous content and the use of a carrier with a wide PSD affects the polarity and the magnitude of the lactose triboelectric charges [26,27].…”

Section: Electrostatic Chargesmentioning

confidence: 99%

Lactose characteristics and the generation of the aerosol

Pilcer¹,

Wauthoz²,

Amighi³

2012

Advanced Drug Delivery Reviews

178

113

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Section: Electrostatic Chargesmentioning

confidence: 99%

Lactose characteristics and the generation of the aerosol

Pilcer¹,

Wauthoz²,

Amighi³

2012

Advanced Drug Delivery Reviews

178

113

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“…This seems to be because the inhalation profile of DPI is affected by various factors including particle size, morphology electrostatic charge and inhalation condition. 10,12,[24][25][26] Therefore, there is a need for preparation and characterization of series of powder samples that are different in surface properties but similar in other properties and compare them under the same inhalation condition.Mechanofusion can modify the surface energy of lactose carrier particles without drastic change of the particle size and can make the particle shape round to lessen the differences.Inverse gas chromatography (IGC) has been utilized to examine the effect of surface energy on the inhalation behavior of DPI. We reported that mechanofusion on a lactose carrier changed the carrier's surface condition and the inhalation properties of DPI formulations containing the lactose carrier and Compound A.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Application and Mechanism of Inhalation Profile Improvement of DPI Formulations by Mechanofusion with Magnesium Stearate

et al. 2008

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Dry powder inhaler (DPI) formulations have been utilized in the treatment of respiratory disease [1][2][3] and for systemic administration.4 -7) They have become common in the inhalation therapy field because of various advantages, such as being free from anti-environmental propellants 8) and ease of use with portable small devices.DPI formulations with fine drug particles and coarse carrier particles have been widely used for a long time. Usually their components are simple and they can be manufactured with conventional equipment. Therefore, they appear to be a valuable option as the formulation for clinical trials, especially in the early stages of development. The carrier particles play the critical role in preventing the agglomeration of fine drug particles which possesses high surface energy due to their large specific surface area. On the other hand, it is necessary to achieve the high deposition in the deep lungs to satisfy the required bioavailability. Because only small particles (aerodynamic diameter below 5 mm) can reach the lungs, fine drug particles should be detached from the coarse carrier particles through the inhalation process. The percentage of small particles to the entire dose is defined as fine particle fraction (FPF). Therefore, FPF is an index of the extent of deposition in the lungs.Studies have been conducted to clarify the factors that control the inhalation properties of the carrier-based DPI formulations. [9][10][11][12][13][14] Many studies focused on the carrier surface properties especially rugosity and/or coverage of high energy binding sites. 10,[15][16][17][18][19][20][21] Surface energy of particles would be one of the major factors influencing the inhalation profile of DPI including FPF. 22,23) However the mechanism of FPF increase has not been fully clarified so far. This seems to be because the inhalation profile of DPI is affected by various factors including particle size, morphology electrostatic charge and inhalation condition. 10,12,[24][25][26] Therefore, there is a need for preparation and characterization of series of powder samples that are different in surface properties but similar in other properties and compare them under the same inhalation condition.Mechanofusion can modify the surface energy of lactose carrier particles without drastic change of the particle size and can make the particle shape round to lessen the differences.Inverse gas chromatography (IGC) has been utilized to examine the effect of surface energy on the inhalation behavior of DPI. We reported that mechanofusion on a lactose carrier changed the carrier's surface condition and the inhalation properties of DPI formulations containing the lactose carrier and Compound A.27) The Andersen cascade impactor (ACI) profile suggested that the increase of FPF was accompanied by the decrease of the interaction between Compound A and carrier particles. Begat et al. also reported that mechanofusion of lactose with Mg-St reduced the interaction between drug and lactose particles.28) Mg-St is known as lubri...

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“…Environmental conditions such as temperature and humidity not only may influence variability of the aerosol generation but also may influence PSD during the process of measurement. Relative humidity will influence triboelectric effects for DPI (32)(33)(34), and together with temperature it will also affect aerosol evaporation during the process of measurement of pMDIs and nebulizers (35). Farzin et al investigated in vitro mouththroat deposition and lung delivery of selected solution and suspension pMDI formulations by using the Alberta Idealized Throat under a range of relative humidity, temperature, and flow rate conditions.…”

Section: Introductionmentioning

confidence: 99%

Effects of Temperature and Humidity on Laser Diffraction Measurements to Jet Nebulizer and Comparison with NGI

Song

Zhan

et al. 2015

AAPS PharmSciTech

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Abstract. Laser diffraction (LD) and next generation impactor (NGI) are commonly used for the evaluation of inhaled drug formulations. In this study, the effect of temperature and humidity on the assessment of the nebulizer particle size distribution (PSD) by LD was investigated, and the consistency between NGI and LD measurements was evaluated. There was an increase in particle size with higher temperature or lower humidity. The particle population with a diameter less than 1 μm was significant at a temperature of 5°C or at relative humidity >90%; however, the same particle population became undetectable when temperature increased to 39°C or at relative humidity of 30-45%. The results of the NGI and LD measurements of aerosol generated from three types of jet nebulizers were compared. A poor correlation between the NGI and LD measurements was observed for PARI LC (2.2 μm) (R 2 = 0.893) and PARI LC (2.9 μm) (R 2 =0.878), while a relatively good correlation (R 2 =0.977) was observed for the largest particle size nebulizer (PARI TIA (8.6 μm)). We conclude that the ambient environment and the nebulizer have significant impacts on the performance and consistency between these instruments. These factors should be controlled in the evaluation of inhaled aerosol drug formulations when these instruments are used individually or in combination.

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Effect of particle morphology on the triboelectrification in dry powder inhalers

Cited by 72 publications

References 19 publications

Lactose characteristics and the generation of the aerosol

Lactose characteristics and the generation of the aerosol

Application and Mechanism of Inhalation Profile Improvement of DPI Formulations by Mechanofusion with Magnesium Stearate

Effects of Temperature and Humidity on Laser Diffraction Measurements to Jet Nebulizer and Comparison with NGI

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