Effect of powder properties on the aerosolization performance of nanoporous mannitol particles as dry powder inhalation carriers

Zhang, Xuejuan; Zhao, Ziyu; Cui, Yingtong; Liu, Fei; Huang, Zhengwei; Huang, Ying; Zhang, Rui; Freeman, Tim; Lu, Xiang-Yun; Pan, Xin; Tan, Wen; Wu, Chuanbin

doi:10.1016/j.powtec.2018.08.058

Cited by 23 publications

(14 citation statements)

References 47 publications

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“…Compared with Sympatec HELOS & INHALER™, particle size obtained from Malvern Mastersizer 2000 was smaller. DPIs was compulsively dispersed by the steel balls of Scirocco 2000 dry powder feeder in Malvern Mastersizer 2000 11 . Thus, particle size determined by Malvern Mastersizer 2000 was the geometry size of particles.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, coarse carriers in the range of 50–200 μm 8 were frequently used to promote the flowability, dispersibility, blend homogeneity of DPIs and reduce the cohesion of micronized APIs 9 . According to a large number of studies, carriers played an important role in the manufacture and usage of DPIs 10 , 11 , 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

“…The pulmonary delivery processes (PDPs) of carrier-based DPIs were proposed based on years of the researches on pulmonary drug delivery system, which could be divided into the following four processes ( Fig. 1 ): fluidization and dispersion of DPIs, transportation of the API‒carrier complex, detachment of APIs from the carriers, and deposition of APIs in the lungs 11 . When DPIs was inhaled, air flow provided the initial kinetic energy, leading to the critical fluidization and dispersion of the DPIs.…”

Section: Introductionmentioning

confidence: 99%

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Novel approach for real-time monitoring of carrier-based DPIs delivery process via pulmonary route based on modular modified Sympatec HELOS

Zhang

Cui

Liang

et al. 2020

Acta Pharmaceutica Sinica B

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An explicit illustration of pulmonary delivery processes (PDPs) was a prerequisite for the formulation design and optimization of carrier-based DPIs. However, the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately, or the approaches merely used a simplified and idealized model. In the present study, a novel modular modified Sympatec HELOS (MMSH) was developed to fully investigate the mechanism of each PDP separately in real-time. An inhaler device, artificial throat and pre-separator were separately integrated with a Sympatec HELOS. The dispersion and fluidization, transportation, detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates. Moreover, time-sliced measurements were used to monitor the PDPs in real-time. The Next Generation Impactor (NGI) was applied to determine the aerosolization performance of the model DPIs. The release profiles of the drug particles, drug aggregations and carriers were obtained by MMSH in real-time. Each PDP of the DPIs was analyzed in detail. Moreover, a positive correlation was established between the total release amount of drug particles and the fine particle fraction (FPF) values ( R 2 = 0.9898). The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs, providing a theoretical basis for the design and optimization of carrier-based DPIs.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel approach for real-time monitoring of carrier-based DPIs delivery process via pulmonary route based on modular modified Sympatec HELOS

Zhang

Cui

Liang

et al. 2020

Acta Pharmaceutica Sinica B

Self Cite

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“…Considering that grinding is a dynamic process and, on the industrial scale, the dry milling process is airflow assisted, the aeration test is regarded adequate and informative for exploring the potential effects of GAs (Zhang et al 2019). Generally, the GA experiments' A-BFE measurements are low compared to the reference test (except for Zalta™ VM1122 -0.03 wt.%).…”

Section: Aerated Testsmentioning

confidence: 99%

Effects of Chemical Additives on Rheological Properties of Dry Ground Ore - a Comparative Study

Chipakwe

Hulme-Smith

Karlkvist

et al. 2021

Mineral Processing and Extractive Metallurgy Review

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It is well documented that chemical additives (grinding aid "GA") during grinding can increase mill throughput, reduce water and energy consumption, narrow the particle size distribution of products, and improve material flowability. These advantages have been linked to their effects on the rheology, although there is a gap in understanding GA effectiveness mechanism on the flow properties. The present study aims to fill this gap using different GAs (Zalta™ GR20-587, Zalta™ VM1122, and sodium hydroxide) through batch grinding experiments of magnetite ore and addressing the mechanisms of their effects on the rheology by an FT4 Powder Rheometer as a unique system. Experimental results showed that GA improved grinding efficiency (energy consumption and product fineness), which were well-correlated with basic flow energy, specific energy, aerated basic flow energy, and aerated energy. Moreover, the rheometry measurement showed strong linear correlations between basic flow energy, specific energy, and the resulting work index when GAs was considered for grinding, which confirmed the effect of GA on ground particles' flowability. Zalta™ VM1122, a polysaccharide-based grinding aid, showed the best performance with 38.8% reduction of basic flow energy, 20.4% reduction of specific energy, 24.6% reduction of aerated basic flow energy, and 38.3% reduction of aerated energy. It also showed the strongest correlation between the grinding parameters and flow parameters (r > 0.93). The present investigation shows a strong indication that the predominant mechanism of GAs is based on the alteration of rheological properties and identify Zalta™ VM1122 as the best GA.

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“…[7] In this context, dry powder inhalers (DPIs) present many advantages over other inhalation devices such as the absence of propellant as well as their solid state conferring better chemical stability compared to liquid and metered dose inhaler aerosols. [8] Furthermore, they do not necessitate any external driving force for their operating and are easier to use for patients since they are portable and do not require coordination between inhalation and actuation. [9][10][11] Recently, emphasis has been placed on the development of dry powder inhalation [9] and a wide range of DPIs is currently available to maximize pulmonary drug delivery with low variability.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of an inhaled antibiotic/adjuvant dry powder combination using an experimental design approach

Douafer

Andrieu

Wafo

et al. 2021

International Journal of Pharmaceutics

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The global increase of multidrug resistant bacteria and the lack of new classes of antibiotic especially those targeting Gram-negative pathogens are leaving the clinicians disarmed to treat numerous bacterial infections. Recently, the design of adjuvants able to enhance antibiotics activities appears to be one of the most promising investigated solutions to circumvent this problem. In this context, we have recently identified a new polyaminoisoprenyl derivative NV716 able to potentiate, at a very low concentration the activity of doxycycline against resistant P. aeruginosa bacterial strains by increasing its intracellular concentration. In this study we will report an experimental protocol to optimize a dry powder for inhalation ensuring the simultaneous delivery of an antibiotic (doxycycline) and an adjuvant (the polyaminoisoprenyl derivative NV716 since aerosol therapy could allow a rapid drug administration and target the respiratory system by avoiding the first pass effect and minimizing undesirable systemic effects. Thus, an experimental design was carried out permitting to identify the influence of several factors on the aerosolization efficiency of our combination and allowing us to find the right composition and manufacture leading to the best optimization of the simultaneous delivery of the two compounds in the form of an inhalable powder. More precisely, the powders of the two active ingredients were prepared by freeze drying and their aerosolization was improved by the addition of carrier particles of lactose inhalation grade. Under these conditions, the best formulation was defined by combining the optimal factors leading to the best aerodynamic properties' values (the lowest MMAD (Mass Median Aerodynamic Diameter) and the highest FPF (Fraction of Fine Particles)) without even using sophisticated engineering techniques. Finally, our results suggest that these molecules could be successfully delivered at the requested concentration in the lungs and then able to decrease drug consumption as well as increase treatment efficacy.

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Effect of powder properties on the aerosolization performance of nanoporous mannitol particles as dry powder inhalation carriers

Cited by 23 publications

References 47 publications

Novel approach for real-time monitoring of carrier-based DPIs delivery process via pulmonary route based on modular modified Sympatec HELOS

Novel approach for real-time monitoring of carrier-based DPIs delivery process via pulmonary route based on modular modified Sympatec HELOS

Effects of Chemical Additives on Rheological Properties of Dry Ground Ore - a Comparative Study

Feasibility of an inhaled antibiotic/adjuvant dry powder combination using an experimental design approach

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