Drug Permeation Characterization of Inhaled Dry Powder Formulations in Air-Liquid Interfaced Cell Layer Using an Improved, Simple Apparatus for Dispersion

Asai, Ayumu; Okuda, Tomoyuki; Sonoda, Erina; Yamauchi, Tomoyo; Kato, Setsuko; Okamoto, Hirokazu

doi:10.1007/s11095-015-1804-1

Cited by 16 publications

(20 citation statements)

References 42 publications

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“…The powders in the tip were dispersed by releasing air compressed in the syringe. 25) Preparation of Dry Powders by Spray-Drying Dry powders were prepared using a spray dryer (SD-1000; Tokyo Rikakikai Co., Ltd., Tokyo, Japan) with a two-fluid nozzle (inner diameter: 0.4 mm). A 1% (w/v) sample solution delivered at a rate of 5 mL/min was atomized at an air pressure of 150 kPa and the droplet was dried at an inlet air temperature of 120°C.…”

Section: Methodsmentioning

confidence: 99%

Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air–Liquid Interface Cultured Cell Layer

Asai

Okuda

Yamauchi

et al. 2016

Biological & Pharmaceutical Bulletin

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Most safety evaluations of dry powder inhalers (DPIs) using cultured cells have been performed with dry powder formulations dissolved in a medium. However, this method is not considered to be suitable to evaluate the safety of inhaled dry powder formulations correctly since it cannot reflect the actual phenomenon on the respiratory epithelial surface. In this study, we established a novel in-vitro safety evaluation system suitable for DPIs by combining an air-liquid interface cultured cell layer and a device for dispersing dry powders, and evaluated the safety of candidate excipients of dry powders for inhalation. The safety of excipients (sugars, amino acids, cyclodextrins, and positive controls) in solutions was compared using submerged cell culture systems with a conventional 96-well plate and Transwell ® . The sensitivity of the cells grown in Transwell ® was lower than that of those grown in the 96-well plate. Dry powders were prepared by spray-drying and we evaluated their safety with a novel in-vitro safety evaluation system using an air-liquid interface cultured cell layer. Dry powders decreased the cell viability with doses more than solutions. On the other hand, dissolving the dry powders attenuated their cytotoxicity. This suggested that the novel in-vitro safety evaluation system would be suitable to evaluate the safety of DPIs with high sensitivity.Key words dry powder; safety evaluation; air-liquid interfaced culture; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; A549 cell Pulmonary drug delivery has been investigated as not only a local treatment for respiratory diseases such as asthma or chronic obstructive pulmonary disease, but also as an alternative route for the systemic delivery of macromolecule drugs such as insulin, calcitonin, and heparin. 1-4)Among the three major systems for pulmonary deliverynebulizers, pressurized metered-dose inhalers (pMDIs), and dry powder inhalers (DPIs)-DPIs have several advantages, including favorable portability, a low cost, and the lack of a need for propellants. Furthermore, the handling of DPIs is easier than that of pMDIs because of breath-actuated passive aerosolization. 5)For effective pulmonary deposition after inhalation, in general, the optimal aerodynamic diameter of drug particles is less than 6 µm.6,7) However, micronized drug particles tend to be highly cohesive and poorly flowable, leading to low-level performance. To solve these problems, it is usual for an excipient, such as coarse lactose monohydrate, to be formulated to physically attach to fine active ingredients. 8,9) It has been recently reported that the addition of amino acids or cyclodextrins (CyDs) as excipients improves pulmonary delivery. 10,11) As for fundamental research on DPIs, evaluation of the physical properties such as particle size and pulmonary deposition is mainstream, whereas biological evaluation such as of the efficacy and safety is essential for clinical application. 12)These biological evaluations of dry powder formulations are often conduct...

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Section: Methodsmentioning

confidence: 99%

Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air–Liquid Interface Cultured Cell Layer

Asai

Okuda

Yamauchi

et al. 2016

Biological & Pharmaceutical Bulletin

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“…The nasal cavity is divided into two by the nasal midline septum with each half opening at the face via nostrils and extending posteriorly to the oral cavity through the nasopharynx 16,19 ( Figure 2). Each cavity consists of anterior and posterior vestibules, respiratory region (containing the superior, the middle and the inferior turbinates) and olfactory region situated at the top.…”

Section: Nasal Anatomymentioning

confidence: 99%

“…There are four types of nasal epithelia in nasal cavity, namely, respiratory, olfactory, squamous (vestibule) and transitional (atrium), being the first two the most important sites of absorption for APIs administered intranasally 19 . The respiratory region is composed by pseudostratified epithelium formed by ciliated and nonciliated columnar cells, mucus-containing goblet cells and basal cells.…”

Section: Nasal Anatomymentioning

confidence: 99%

“…The trigeminal nerve, or the fifth (V) cranial nerve, is the largest of the twelve cranial nerves and its distribution and nasal passage innervation are well understood 19 . In addition to the olfactory pathway, transport to the CNS can also take place via a trigeminal nerve pathway, along the peripheral ophthalmic branch (V1) of trigeminal nerves located at the respiratory region.…”

Section: Trigeminal Pathwaymentioning

confidence: 99%

“…It is recognised that size is a vital feature of the particles used in the delivery of API's as it influences almost every aspect of their functions, such as drug load capacity, route of administration, dissolution and absorption rates, flow properties, stability or uptake and clearance mechanisms 18 . On the other hand, morphology is also a parameter that could have a major impact on the carrier's performance, like degradation, transport or targeting, and therefore is a feature that should be studied 19 .…”

Section: Introductionmentioning

confidence: 99%

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Overcoming central nervous system-barriers by the development of hybrid structured systems for nose-to-brain drug delivery using clean technologies

Gonçalves¹

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Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

Dong

Zhou

et al. 2020

Acta Pharmaceutica Sinica B

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Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein–phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

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Drug Permeation Characterization of Inhaled Dry Powder Formulations in Air-Liquid Interfaced Cell Layer Using an Improved, Simple Apparatus for Dispersion

Cited by 16 publications

References 42 publications

Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air–Liquid Interface Cultured Cell Layer

Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air–Liquid Interface Cultured Cell Layer

Overcoming central nervous system-barriers by the development of hybrid structured systems for nose-to-brain drug delivery using clean technologies

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

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