Comparative Assessment of In Vitro and In Silico Methods for Aerodynamic Characterization of Powders for Inhalation

Ignjatović, Jelisaveta; Šušteršič, Tijana; Bodić, Aleksandar; Cvijić, Sandra; Đuriš, Jelena; Rossi, Alessandra; Dobričić, Vladimir; Ibrić, Svetlana; Filipović, Nenad

doi:10.3390/pharmaceutics13111831

Cited by 8 publications

(6 citation statements)

References 59 publications

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“…It can be concluded that the DPI device considered in this study has a lower percentage of total deposited particles (higher efficiency) than the devices from the literature at an airflow rate of 60 l/min. In addition, the in vitro results presented in [25] showed a 13-17% particle deposition for the same DPI formulation, meaning that the results from the CFD-DPM simulations correspond well to the in vitro results. In relation to the definition of particle behavior as a result of drag and adhesion moment values, Figure 9 shows the drag and adhesion moment values for the same particle ID for COR_normal = 0.75 and COR_tangential = 0.75.…”

Section: Resultssupporting

confidence: 64%

“…Although several papers [9,13,20] investigated the behavior of particles inside the DPIs and particle wall collision, there are no published studies investigating whether a particle rebounds after impacting a wall. Our previous publication [25] compares in vitro and in silico methods for DPI aerodynamic characterization, with the goal of comparing the results of the CFD-DPM simulations with the results of three in vitro methods for the DPI aerodynamic assessment of solid lipid microparticles. In the current study, we focus on the development of CFD-DPM methods to investigate the particle detachment process (sliding and rolling), including the fluid dynamic interaction between the flow and the particles stuck to the wall, by defining equations to describe the sticking and rebounding (sliding and rolling) mechanisms.…”

Section: Related Workmentioning

confidence: 99%

“…The device geometry was created based on the real DPI device. The DPI device considered in this paper was an RS01 ® inhaler, which was used in our previous research [25]. The inhaler geometry was obtained using commercial CAD software designed for these purposes (i.e., CATIA version 5, Dassault Systems, France), and is shown in Figure 1.…”

Section: Geometry and Meshingmentioning

confidence: 99%

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Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler

et al. 2022

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The development of novel dry powders for dry powder inhalers (DPIs) requires the in vitro assessment of DPI aerodynamic performance. As a potential complementary method, in silico numerical simulations can provide additional information about the mechanisms that guide the particles and their behavior inside DPIs. The aim of this study was to apply computational fluid dynamics (CFDs) coupled with a discrete phase model (DPM) to describe the forces and particle trajectories inside the RS01® as a model DPI device. The methodology included standard fluid flow equations but also additional equations for the particle sticking mechanism, as well as particle behavior after contacting the DPI wall surface, including the particle detachment process. The results show that the coefficient of restitution between the particle and the impact surface does not have a high impact on the results, meaning that all tested combinations gave similar output efficiencies and particle behaviors. No sliding or rolling mechanisms were observed for the particle detachment process, meaning that simple bouncing off or deposition particle behavior is present inside DPIs. The developed methodology can serve as a basis for the additional understanding of the particles’ behavior inside DPIs, which is not possible using only in vitro experiments; this implies the possibility of increasing the efficiency of DPIs.

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Section: Resultssupporting

confidence: 64%

Section: Related Workmentioning

confidence: 99%

Section: Geometry and Meshingmentioning

confidence: 99%

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Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler

et al. 2022

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“…The results obtained here were in accordance with the patterns identified by the in vitro measurements. However, the in silico models can show lower lung deposition values compared to the in vitro methods (i.e., ACI) [ 55 ]. The high extra-thoracic (ET), upper airways, and deposition results here were due to the shorter inhalation time used (2.04 s), which is half the inhalation time that was used in ACI.…”

Section: Resultsmentioning

confidence: 99%

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

Banat,

Csóka,

Paróczai

et al. 2024

Pharmaceuticals

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Pulmonary inflammations such as chronic obstructive pulmonary disease and cystic fibrosis are widespread and can be fatal, especially when they are characterized by abnormal mucus accumulation. Inhaled corticosteroids are commonly used for lung inflammations despite their considerable side effects. By utilizing particle engineering techniques, a combined dry powder inhaler (DPI) comprising nanosized ketoprofen-embedded mannitol-coated microparticles was developed. A nanoembedded microparticle system means a novel advance in pulmonary delivery by enhancing local pulmonary deposition while avoiding clearance mechanisms. Ketoprofen, a poorly water-soluble anti-inflammatory drug, was dispersed in the stabilizer solution and then homogenized by ultraturrax. Following this, a ketoprofen-containing nanosuspension was produced by wet-media milling. Furthermore, co-spray drying was conducted with L-leucine (dispersity enhancer) and mannitol (coating and mucuactive agent). Particle size, morphology, dissolution, permeation, viscosity, in vitro and in silico deposition, cytotoxicity, and anti-inflammatory effect were investigated. The particle size of the ketoprofen-containing nanosuspension was ~230 nm. SEM images of the spray-dried powder displayed wrinkled, coated, and nearly spherical particles with a final size of ~2 µm (nano-in-micro), which is optimal for pulmonary delivery. The mannitol-containing samples decreased the viscosity of 10% mucin solution. The results of the mass median aerodynamic diameter (2.4–4.5 µm), fine particle fraction (56–71%), permeation (five-fold enhancement), and dissolution (80% release in 5 min) confirmed that the system is ideal for local inhalation. All samples showed a significant anti-inflammatory effect and decreased IL-6 on the LPS-treated U937 cell line with low cytotoxicity. Hence, developing an innovative combined DPI comprising ketoprofen and mannitol by employing a nano-in-micro approach is a potential treatment for lung inflammations.

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“…By conducting this test, the uniformity and spread of the spray could be visually examined and analysed for consistency and effectiveness. 24 …”

Section: Methodsmentioning

confidence: 99%

Fabrication and in vitro characterization of curcumin film-forming topical spray: An integrated approach for enhanced patient comfort and efficacy

Shetty,

Dubey,

Chrystle

et al. 2024

F1000Res

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Background Curcumin, known for its anti-inflammatory properties, was selected for the developing consumer friendly film forming spray that offers precise delivery of curcumin and and improves patient adherence. Methods An optimized film-forming solution was prepared by dissolving curcumin (1%), Eudragit RLPO (5%), propylene glycol (1%), and camphor (0.5%) in ethanol: acetone (20:80) as the solvent. The solution was filled in a spray container which contained 70% solutions and 30% petroleum gas. In-vitro characterization was performed. Results Potential anti-inflammatory phytoconstituents were extracted from the PubChem database and prepared as ligands, along with receptor molecules (nsp10-nsp16), for molecular docking using Autodock Vina. The docking study showed the lowest binding energy of -8.2 kcal/mol indicates better binding affinities. The optimized formulation consisted of ethanol:acetone (20:80) as the solvent, Eudragit RLPO (5%) as the polymer, propylene glycol (1%) as the plasticizer, and camphor oil (0.5%) as the penetration enhancer. The optimized formulation exhibited pH of 5.8 ± 0.01, low viscosity, low film formation time (19.54 ± 0.78 sec), high drug content (8.243 ± 0.43 mg/mL), and extended ex vivo drug permeation (85.08 ± 0.09%) for nine hours. Consequently, the formulation was incorporated into a container using 30% liquefied petroleum gas, delivering 0.293 ± 0.08 mL per actuation, containing 1.53 ± 0.07 mg of the drug. The film-forming spray exhibited higher cumulative drug permeation (83.94 ± 0.34%) than the marketed cream formulation and pure drug solution after 9 h, with an enhancement ratio of 14. Notably, the film-forming spray exhibited no skin irritation and remained stable for over three months. Conclusions The developed curcumin film-forming system is promising as a carrier for wound management because of its convenient administration and transport attributes. Further in vivo studies are required to validate its efficacy in wound management.

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Comparative Assessment of In Vitro and In Silico Methods for Aerodynamic Characterization of Powders for Inhalation

Cited by 8 publications

References 59 publications

Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler

Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

Fabrication and in vitro characterization of curcumin film-forming topical spray: An integrated approach for enhanced patient comfort and efficacy

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