Fluorescence-enabled evaluation of nasal tract deposition and coverage of pharmaceutical formulations in a silicone nasal cast using an innovative spray device

D’Angelo, Davide; Kooij, Ernst S.; Verhoeven, Frank; Sonvico, Fabio; Rijn, C.J.M. van

doi:10.1016/j.jare.2022.04.011

Cited by 10 publications

(10 citation statements)

References 22 publications

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“…Deposition experiments were performed to determine the deposition characteristics of the nanotech nebulization chip under different conditions. The experimental procedures of the deposition study were adapted from D’Angelo et al [ 9 ]. A transparent silicone nasal cavity model (Model LM-005 Koken Ltd., Tokyo, Japan) was used to simulate the nasal cavity.…”

Section: Methodsmentioning

confidence: 99%

“…This is surprising as experimental studies have shown that many spray pump devices deposit a significant amount of the drug in the nasal valve and vestibule, which are considered less active regions of the nasal cavity [ 6 , 7 , 8 ]. This deposition in the nasal valve and vestibule is likely due to inertial impaction since most spray pumps are designed to release a large proportion of aerosol particles substantially larger than 50 μm, which exit the devices at a high speed [ 9 ]. Several studies have suggested that nasal nebulization with much smaller droplets (<50 μm) is a more effective method of delivering topical medication beyond the nasal valve region than aqueous spray pumps [ 4 , 5 , 7 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this research, we performed an in vitro deposition study to investigate the extent of theophylline deposition in the olfactory region using a novel nanotech nozzle chip in combination with a simple spray pump. The nanotech nozzle chip consists of a silicon chip with micrometer-sized pores, which emits a slow-moving spray cloud upon spraying with smaller droplets and a narrower droplet size distribution than the conventional swirl nozzle [ 9 ]. It is made with semi-conductor technology, which provides several advantages for production in addition to the potential improvements in the nasal deposition investigated in this work.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Improved Olfactory Deposition of Theophylline Using a Nanotech Soft Mist Nozzle Chip

Zhang,

Verhoeven,

Ravensbergen

et al. 2023

Pharmaceutics

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Currently, nasal administration of active pharmaceutical ingredients is most commonly performed using swirl-nozzle-based pump devices or pressurized syringes. However, they lead to limited deposition in the more active regions of the nasal cavity, especially the olfactory region, which is crucial for nose-to-brain drug delivery. This research proposes to improve deposition in the olfactory region by replacing the swirl nozzle with a nanoengineered nozzle chip containing micrometer-sized holes, which generates smaller droplets of 10–50 μm travelling at a lower plume velocity. Two nanotech nozzle chips with different hole sizes were tested at different inhalation flow rates to examine the deposition patterns of theophylline, a hyposmia treatment formulation, using a nasal cavity model. A user study was also conducted and showed that the patient instructions influenced the inhalation flow rate characteristics. Targeted flow rates of between 0 and 25 L/min were used for the in vitro deposition study, yielding 21.5–31.5% olfactory coverage. In contrast, the traditional swirl nozzle provided only 10.8% coverage at a similar flow rate. This work highlights the potential of the nanotech soft mist nozzle for improved intranasal drug delivery, particularly to the olfactory region.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Improved Olfactory Deposition of Theophylline Using a Nanotech Soft Mist Nozzle Chip

Zhang,

Verhoeven,

Ravensbergen

et al. 2023

Pharmaceutics

Self Cite

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“…Stefan Kooij 1* , Cees van Rijn 1 , Neil Ribe 2 & Daniel Bonn 1 The charging of poorly conducting liquids due to flows is a well-known phenomenon, yet the precise charging mechanism is not fully understood. This is especially relevant for sprays, where the spray plume dynamics and maximum distance travelled of a spray dramatically changes for different levels of charging: charging of the droplets makes them repel, thereby preventing drop coalescence and altering the shape of the spray plume.…”

Section: Self-charging Of Spraysmentioning

confidence: 99%

“…Spray plume dynamics are important for many applications such as drug delivery 1,2 , health and bodycare, perfumes, agriculture, but also in the spreading of pathogens such as SARS-CoV-2 3,4 . When poorly conducting liquids are used, interaction of the flow with the nozzle can lead to self-charging.…”

Section: Self-charging Of Spraysmentioning

confidence: 99%

Self-charging of sprays

Kooij

Rijn

Ribe

et al. 2022

Sci Rep

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The charging of poorly conducting liquids due to flows is a well-known phenomenon, yet the precise charging mechanism is not fully understood. This is especially relevant for sprays, where the spray plume dynamics and maximum distance travelled of a spray dramatically changes for different levels of charging: charging of the droplets makes them repel, thereby preventing drop coalescence and altering the shape of the spray plume. As the charging depends on many factors including the flow and the interactions between the liquid and the nozzle, many models and scaling laws exist in the literature. In this work we focus on perhaps the simplest flow regime, laminar jets created by ultra short channels, and quantify the charging as a function of the different parameters. We present a simple model that collapses all the data for over 4 orders of magnitude difference in streaming currents for various nozzle sizes, flow velocities and surface treatments. We further show that the charging polarity can even be reversed by applying an oppositely charged coating to the nozzle, an important step for any application.

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Amorphous nasal powder advanced performance: in vitro/ex vivo studies and correlation with in vivo pharmacokinetics

Henriques,

Bicker,

Carona

et al. 2023

J. Pharm. Investig.

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Purpose Amorphous solid dispersions (ASD) for nasal delivery offer the opportunity to increase drug release performance, while using polymers with mucoadhesive properties. The aim of the present study was to apply this solubility enhancement technique to a poorly soluble drug for nasal delivery, while comparing two particle engineering strategies, namely spray dried microparticles and chimeral agglomerates, with the corresponding physical blends with crystalline drug. Methods Formulations of piroxicam were manufactured using varied polymer and particle engineering strategies and evaluated through in vitro drug release and ex vivo permeation studies, as well as nasal deposition and in vivo pharmacokinetic studies. Results ASD with hydroxypropyl methylcellulose (HPMC) showed enhanced drug release and permeation, compared to polyvinylpyrrolidone/vinyl acetate formulations and blends. Nasal deposition of HPMC chimeral agglomerates suggested off-target deposition. In vivo pharmacokinetic studies revealed that spray-dried HPMC-containing microparticles exhibited the highest maximum plasma concentration (Cmax) and the lowest time to attain it (tmax). In vitro release rate and in vivo absorption rate were correlated as well as tmax and in vitro performance. When excluding the formulation with least nasal targeted deposition, in vitro release and ex vivo permeation performance were also correlated with Cmax and area under the drug concentration-time curve (AUC) from 0 to 1 h, with R2 > 0.89. Conclusion ASD for nasal delivery provide fast drug absorption, which depends on the supersaturation ability of the polymer employed. In vitro-in vivo correlations suggested that in vitro release and ex vivo permeation studies are predictive tools regarding nasal absorption.

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Fluorescence-enabled evaluation of nasal tract deposition and coverage of pharmaceutical formulations in a silicone nasal cast using an innovative spray device

Cited by 10 publications

References 22 publications

Improved Olfactory Deposition of Theophylline Using a Nanotech Soft Mist Nozzle Chip

Improved Olfactory Deposition of Theophylline Using a Nanotech Soft Mist Nozzle Chip

Self-charging of sprays

Amorphous nasal powder advanced performance: in vitro/ex vivo studies and correlation with in vivo pharmacokinetics

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