Linking carrier morphology to the powder mechanics of adhesive mixtures for dry powder inhalers via a blend-state model

Rudén, Jonas; Frenning, Göran; Bramer, Tobias; Thalberg, Kyrre; An, Junxue; Alderborn, Göran

doi:10.1016/j.ijpharm.2019.02.038

Cited by 28 publications

(10 citation statements)

References 29 publications

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“…All carriers (starting material, wet-sieved and spray-congealed ones) were blended with 1 wt% BDP (binary mixtures) and additionally, with a controlled amount of fines, namely 0.2 wt% MgSt and 10 wt% of 'Preblend' (fine α-LH + MgSt) (ternary mixtures). It is, generally, reported that rough and irregular carrier particles have a higher loading capacity compared to smooth ones (37). In more rough/irregular particles, the higher number of indentations and cavities present, allow a greater number of fine particles to fill and/or coat the surface of the carrier.…”

Section: Impact Of Particle Engineering On Dpi Performancementioning

confidence: 99%

“…On the contrary, the less corrugated two α-LH materials (Cap60 and Cap60_WS) could not accommodate the fines as efficiently, leading to segregation (between coarse carrier particles hosting fines and particulate agglomerates of fines, see supplementary material Fig. S2 (c) and (f)) (37). Thus, powder flow was deteriorated and an increase in inter-and intradevice variability was seen.…”

Section: Impact Of Particle Engineering On Shot Weight Consistencymentioning

confidence: 99%

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Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance

et al. 2021

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Purpose Traditionally, α-lactose monohydrate is the carrier of choice in dry powder inhaler (DPI) formulations. Nonetheless, other sugars, such as D-mannitol, have emerged as potential alternatives. Herein, we explored different particle engineering processes to produce D-mannitol carriers for inhaled delivery. Methods Wet-sieving and spray-congealing were employed as innovative techniques to evaluate the impact of engineering on the particle properties of D-mannitol. To that end, the resulting powders were characterized concerning their solid-state, micromeritics and flowability. Afterwards, the engineered carrier particles were blended with inhalable size beclomethasone dipropionate to form low dose (1 wt%) DPI formulations. The in vitro aerosolization performance was evaluated using the NEXThaler®, a reservoir multi-dose device. Results Wet-sieving generated D-mannitol particles with a narrow particle size distribution and spray-congealing free-flowing spherical particles. The more uniform pumice particles with deep voids and clefts of wet-sieved D-mannitol (Pearl300_WS) were beneficial to drug aerosolization, only when used in combination with a ternary agent (10 wt% of ‘Preblend’). When compared to the starting material, the spray-congealed D-mannitol has shown to be promising in terms of the relative increase of the fine particle fraction of the drug (around 100%), when used without the addition of ternary agents. Conclusions The wet-sieving process and the related aerosolization performance are strongly dependent on the topography and structure of the starting material. Spray-congealing, has shown to be a potential process for generating smooth spherical particles of D-mannitol that enhance the in vitro aerosolization performance in binary blends of the carrier with a low drug dose.

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Section: Impact Of Particle Engineering On Dpi Performancementioning

confidence: 99%

Section: Impact Of Particle Engineering On Shot Weight Consistencymentioning

confidence: 99%

Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance

et al. 2021

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“…This could be attributed to the rough and wavy surface of the porous and spherical SFD carrier with small and shallow indentations. Such indentations were not deep enough to hold large amounts of small drug particles on the SFD carrier, therefore more irregularities associated with larger surface areas (Kaialy 2016;Rudén, et al 2019). This would have kept the GLP-1 particles relatively separated by providing more contact areas available for drug-carrier adhesion.…”

Section: Scanning Electron Microscopymentioning

confidence: 99%

Development of drug alone and carrier-based GLP-1 dry powder inhaler formulations

Babenko

Alany

Calabrese

et al. 2022

International Journal of Pharmaceutics

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“…In general, there were two types of DPIs, carrier-based DPIs and carrier-free DPIs. To achieve desirable pulmonary delivery efficiency, the active pharmaceutical ingredients (APIs) required micronization to achieve an aerodynamic diameter ( d ae ) of 0.5–5 μm 8 . However, the micronized APIs were prone to be cohesive, resulting in deterioration of flowability and dispersibility 9 .…”

Section: Introductionmentioning

confidence: 99%

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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Linking carrier morphology to the powder mechanics of adhesive mixtures for dry powder inhalers via a blend-state model

Cited by 28 publications

References 29 publications

Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance

Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance

Development of drug alone and carrier-based GLP-1 dry powder inhaler formulations

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

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