Application of supercritical fluid to preparation of powders of high-molecular weight drugs for inhalation

Okamoto, Hirokazu; Danjo, Kazumi

doi:10.1016/j.addr.2007.02.002

Cited by 70 publications

(34 citation statements)

References 80 publications

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“…The resulting cake is composed of the protein, any nonvolatile excipients, and a small amount of residual water tightly associated with the protein Time consuming Broad particle size distribution e.g. trehalose, inulin, dextran [6,11] Spray drying Uses atomization to form microdispersed droplets. The water in these droplets quickly evaporates when passed through a stream of hot gas, resulting in the formation of a fine powder of microparticles containing protein and excipients Degradation Low process efficacy…”

Section: Jet Millingmentioning

confidence: 99%

“…leucine, lactose, trehalose, dipamitoylphosphatidylcholine (DPPC), albumin [8,11,22,24,25] Spray-freeze drying…”

Section: Jet Millingmentioning

confidence: 99%

“…e.g. sucrose, trehalose, manitol [2,8,11,13] trifluoromethane, chlorodifluoromethane, diethyl ether, water, or CO 2 with ethanol [13]. In addition SCF possess several fundamental advantages as solvents and/or anti-solvents for processing heat-labile solutes at low temperature.…”

Section: Jet Millingmentioning

confidence: 99%

“…Thorough discussions of differences in the above techniques have been recently published elsewhere [8][9][10][11][12][13]. This review proposes to present an up-to-date outlook on the progression of dry powder formulations for inhalation of macromolecules using SCF techniques, covering its challenges, possibilities and recent developments.…”

Section: Jet Millingmentioning

confidence: 99%

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Recent Advances Using Supercritical Fluid Techniques for Pulmonary Administration of Macromolecules via Dry Powder Formulations

Alfagih¹,

Alanazi²,

Hutcheon³

et al. 2011

DDL

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Growing demands on a suitable formulation method that ensures the stability of the active compound coupled with the limitations of current methods (milling, lyophilization, spray drying, and freeze spray drying) has brought wide attention to supercritical fluid (SCF) technology. Advantages of using the SCF technology comprise its high abilities, adaptability in providing alternative processing methods, high compressibility and diffusivity of the supercritical fluid, capability as an alternative for conventional organic solvents, and the option to attain different processing parameters which would be otherwise difficult to conduct with traditional methods. This review proposes to present an up-to-date outlook on dry powder pulmonary formulations of macromolecules using SCF technology.

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Section: Jet Millingmentioning

confidence: 99%

“…leucine, lactose, trehalose, dipamitoylphosphatidylcholine (DPPC), albumin [8,11,22,24,25] Spray-freeze drying…”

Section: Jet Millingmentioning

confidence: 99%

Section: Jet Millingmentioning

confidence: 99%

Section: Jet Millingmentioning

confidence: 99%

See 2 more Smart Citations

Recent Advances Using Supercritical Fluid Techniques for Pulmonary Administration of Macromolecules via Dry Powder Formulations

Alfagih¹,

Alanazi²,

Hutcheon³

et al. 2011

DDL

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“…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.…”

mentioning

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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Polymer‐based Delivery Systems for the Pulmonary Delivery of Biopharmaceuticals

Kunda

Alfagih

Saleem

et al. 2015

Pulmonary Drug Delivery

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Application of supercritical fluid to preparation of powders of high-molecular weight drugs for inhalation

Cited by 70 publications

References 80 publications

Recent Advances Using Supercritical Fluid Techniques for Pulmonary Administration of Macromolecules via Dry Powder Formulations

Recent Advances Using Supercritical Fluid Techniques for Pulmonary Administration of Macromolecules via Dry Powder Formulations

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

Polymer‐based Delivery Systems for the Pulmonary Delivery of Biopharmaceuticals

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