A Novel Apparatus for Rat in Vivo Evaluation of Dry Powder Formulations for Pulmonary Administration

Okamoto, Hirokazu; Aoki, Makiko; Danjo, Kazumi

doi:10.1002/1520-6017(200008)89:8<1028::aid-jps7>3.0.co;2-3

Cited by 35 publications

(16 citation statements)

References 26 publications

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“…All animals were observed for mortality, general condition and potential clinical signs. The endotracheal apparatus was similar to previous study (Okamoto et al, 2000).…”

Section: Animal Studysupporting

confidence: 93%

Inhalable, large porous PLGA microparticles loaded with paclitaxel: preparation,in vitroandin vivocharacterization

Alipour

Montaseri

Tafaghodi

2015

Journal of Microencapsulation

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Large porous particles (LPPs) could be used as a useful carrier for non-invasive delivery to the deep lung. Pulmonary delivery of paclitaxel-loaded LPPs (PTX-LPPs) can help to eliminate the highly complicated and harmful solvent used in PTX parenteral formulations. PTX-LPPs with mass median aerodynamic diameter (MMAD) of 5.74 ± 0.09 μm, high encapsulation efficiency and good aerosolisation properties were produced using ammonium bicarbonate as porogen. Cytotoxicity of PTX-LPPs on A549 and Calu-6 cell lines was comparable with Free-PTX. Endotracheal administration of PTX-LPPs in rats exhibited PTX plasma concentration in the therapeutic range which lasted 4-fold longer than i.v. injection. The bioavailability was measured as 51 ± 7.1%. The lung targeting efficiency (Te) of PTX-LPPs was 11.9-fold higher than i.v. administration. PTX-LPPs could deliver a higher PTX to lung with a non-toxic plasma level in a longer duration which shows their pulmonary delivery suitability.

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“…All animals were observed for mortality, general condition and potential clinical signs. The endotracheal apparatus was similar to previous study (Okamoto et al, 2000).…”

Section: Animal Studysupporting

confidence: 93%

Inhalable, large porous PLGA microparticles loaded with paclitaxel: preparation,in vitroandin vivocharacterization

Alipour

Montaseri

Tafaghodi

2015

Journal of Microencapsulation

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“…[1][2][3][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.…”

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confidence: 93%

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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“…The results obtained in the present study are consistent with the findings reported by others (23,24) that the dry powders are more efficacious than solution formulation for pulmonary delivery of proteins. Okamoto et al (23) have shown that spray-dried insulin when delivered as a powder was more effective than the spray-dried solution in reducing plasma glucose values in anesthetized rats.…”

Section: Pulmonary Absorption Studiesmentioning

confidence: 99%

Inhaled Insulin is Better Absorbed When Administered as a Dry Powder Compared to Solution in the Presence or Absence of Alkylglycosides

Hussain

Majumder²,

Ahsan

2006

Pharm Res

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A Novel Apparatus for Rat in Vivo Evaluation of Dry Powder Formulations for Pulmonary Administration

Cited by 35 publications

References 26 publications

Inhalable, large porous PLGA microparticles loaded with paclitaxel: preparation,in vitroandin vivocharacterization

Inhalable, large porous PLGA microparticles loaded with paclitaxel: preparation,in vitroandin vivocharacterization

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

Inhaled Insulin is Better Absorbed When Administered as a Dry Powder Compared to Solution in the Presence or Absence of Alkylglycosides

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