Tailoring the flow properties of inhaled micronized drug powders by atomic and molecular layer deposition

Zhang, Fuweng; Wu, Kai; Zara, Damiano La; Sun, Feilong; Quayle, Michael J.; Petersson, Gunilla; Folestad, Staffan; Chew, Jia Wei; Ommen, J. Ruud van

doi:10.1016/j.cej.2023.142131

Cited by 5 publications

(4 citation statements)

References 51 publications

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“…Inhalation formulations are a class of ultrafine pharmaceutical powders with particle size requirements ranging from 0.5 to 10 μm . As an advanced formulation, it possesses exceptional properties including rapid onset of action, precise targeting, effective dosage, and high activity .…”

Section: Introductionmentioning

confidence: 99%

“…Inhalation formulations are a class of ultrafine pharmaceutical powders with particle size requirements ranging from 0.5 to 10 μm. 1 As an advanced formulation, it possesses exceptional properties including rapid onset of action, 2 precise targeting, 3 effective dosage, 4 and high activity. 5 These attributes significantly enhance the dissolution and bioavailability of insoluble pharmaceuticals while improving patient compliance and reducing toxicity and side effects to the respiratory tract in treating chronic respiratory diseases and systemic diseases.…”

Section: Introductionmentioning

confidence: 99%

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A Scalable Freeze-Dissolving Approach to Prepare Ultrafine Crystals for Inhalation: Mechanism and Validation

Guo,

Cao,

Zhang

et al. 2024

Crystal Growth & Design

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Inhaled drug delivery has garnered increasing attention due to its inherent advantages including rapid onset of action, targeted delivery, high bioavailability, and reduced side effects, which holds promise for the treatment of localized lung diseases and systemic diseases. The currently dominant technologies for the preparation of inhalants are air flow pulverization, media milling, and spray drying, which encounter challenges such as inaccurate particle size control, inefficiency, instability, and difficulties in scaling up. The present study proposes a freezedissolving technique (FDT) for the preparation of inhalable microcrystals, comprising two essential steps: rapid freezing of microdroplets into iced pellets within seconds and subsequent dissolution of a solvent in the iced pellets to release the microcrystals in a suspension. By employing the FDT technique, griseofulvin, a representative inhalant, was successfully engineered into a bipyramidal morphology with a targeted particle size (<5 μm), minimal agglomeration (<3%), and an aspect ratio below 2, in which the solvent and stabilizer systems played pivotal roles in facilitating or impeding nucleation and crystal growth processes. To verify the universality of the FDT, six other typical inhalant preparation processes were successfully developed based on the FDT with a controllable crystal size between 1 and 10 μm. Furthermore, three out of the aforementioned seven model substances were randomly selected, and their preparation was scaled up by a factor of 100, yielding consistent results with those obtained at a smaller test scale. This study outlines the freeze-dissolving mechanism in ultrafine crystal formation and demonstrates that the FDT is a robust and scalable approach for the production of inhalants.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Scalable Freeze-Dissolving Approach to Prepare Ultrafine Crystals for Inhalation: Mechanism and Validation

Guo,

Cao,

Zhang

et al. 2024

Crystal Growth & Design

View full text Add to dashboard Cite

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“…8 Additionally, MLD has potential applications for drug delivery systems in the biomedical field. 9 Organic−inorganic hybrid films, called metalcones, are grown by alternating the self-limiting chemisorption of metal precursors and multifunctional organic alcohols. 10,11 Metalcones are classified as a type of metal alkoxides and have several variants such as alucones, 6,12−16 zincones, 17−19 titanicones, 20−23 and hafnicones.…”

Section: Introductionmentioning

confidence: 99%

“…The unique features of MLD make it a promising method for the fabrication of ultrathin films with tailored properties and functionality. , For example, MLD has been used to prepare protective coatings for electronic devices, gas permeation barriers, and functional materials for energy storage and conversion . Additionally, MLD has potential applications for drug delivery systems in the biomedical field …”

Section: Introductionmentioning

confidence: 99%

Origin of Instability of Titanicone Grown by Molecular Layer Deposition Using TiCl₄ and Ethylene Glycol

Kim,

Hyun,

Kim

et al. 2023

Chem. Mater.

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Titanicone, obtained through molecular layer deposition (MLD) using TiCl 4 and ethylene glycol (EG), is often regarded as a thin film of titanium ethylene glycolate [Ti(OCH 2 CH 2 O) 2 ]. Nevertheless, titanicone exhibits a distinct vulnerability to moisture, while single crystals of Ti(OCH 2 CH 2 O) 2 remain stable, even in the presence of water. To elucidate the origin of instability, we investigated the pathway of chemical degradation for titanicone using in situ and ex situ analytical methods such as Fourier transform infrared spectrometry, quartz crystal microbalance, quadrupole mass spectrometry, and X-ray photoelectron spectroscopy. Our analyses unveiled that the instability of the MLD-grown titanicone film in the presence of water can be primarily attributed to the high chlorine content present as Ti−Cl species and the coexistence of single-reacted EG species as well as double-reacted EG species, unlike in Ti(OCH 2 CH 2 O) 2 crystals. Water molecules react with the Ti−Cl species, leading to the formation of Ti−OH species and the release of HCl gas. Furthermore, the single-reacted EG species undergo an intramolecular cyclization reaction catalyzed by HCl, resulting in the formation of Ti−OH and the liberation of ethylene oxide. Consequently, when exposed to water, the MLD-grown titanicone turns into a water-stable mixed film composed of TiO 2 and Ti(OCH 2 CH 2 O) 2 .

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Multiscale computational fluid dynamics modelling of spatial ALD on porous li-ion battery electrodes

Li,

Chen,

Nie

et al. 2024

Chemical Engineering Journal

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Tailoring the flow properties of inhaled micronized drug powders by atomic and molecular layer deposition

Cited by 5 publications

References 51 publications

A Scalable Freeze-Dissolving Approach to Prepare Ultrafine Crystals for Inhalation: Mechanism and Validation

A Scalable Freeze-Dissolving Approach to Prepare Ultrafine Crystals for Inhalation: Mechanism and Validation

Origin of Instability of Titanicone Grown by Molecular Layer Deposition Using TiCl₄ and Ethylene Glycol

Multiscale computational fluid dynamics modelling of spatial ALD on porous li-ion battery electrodes

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Tailoring the flow properties of inhaled micronized drug powders by atomic and molecular layer deposition

Cited by 5 publications

References 51 publications

A Scalable Freeze-Dissolving Approach to Prepare Ultrafine Crystals for Inhalation: Mechanism and Validation

A Scalable Freeze-Dissolving Approach to Prepare Ultrafine Crystals for Inhalation: Mechanism and Validation

Origin of Instability of Titanicone Grown by Molecular Layer Deposition Using TiCl4 and Ethylene Glycol

Multiscale computational fluid dynamics modelling of spatial ALD on porous li-ion battery electrodes

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Product

Resources

About

Origin of Instability of Titanicone Grown by Molecular Layer Deposition Using TiCl₄ and Ethylene Glycol