Particle Size Analysis of Aerosols from Medicinal                    Inhalers

Mitchell, Jolyon; Nagel, Mark

doi:10.14356/kona.2004010

Cited by 66 publications

(75 citation statements)

References 102 publications

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“…In the absence of more rapid multistage impactor-based techniques, so-called realtime APS is commonly used according to the time-of-flight principle. [15][16][17][18] This instrument typically allows measurements of particle sizes within a minute and may therefore be suitable for screening the inhalation properties of expensive APIs, including siRNAs.…”

Section: Effects Of N-sirna Concentrations and Nebulizer Types On Mmamentioning

confidence: 99%

Inhalation Properties and Stability of Nebulized Naked siRNA Solution for Pulmonary Therapy

2016

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The use of naked unmodified small interfering RNA (N-siRNA) without vector has previously been investigated as a pulmonary therapy. However, little is known regarding stabilities and aerodynamic particle sizes of N-siRNA-containing droplets; nebulizers have not yet been optimized for N-siRNA solutions. Thus, in this study, we investigated the feasibility of inhaled N-siRNA solutions for pulmonary therapy using nebulization. Various nebulizers and N-siRNA concentrations were assessed in terms of siRNA integrity after nebulization, and inhalation properties including aerodynamic particle size were examined. In comparison with ultrasonic-, air-jet-, and vibrating-mesh nebulizers, N-siRNA integrity was not affected by nebulization. Thus, in further experiments, performances of N-siRNA aerosols with different nebulizers and N-siRNA concentrations were evaluated and screened using an aerodynamic particle sizer (APS) which employed the time-of-flight principle or a cascade impactor. Mean mass aerodynamic diameters of N-siRNA-containing droplets from vibrating-mesh nebulizers tended to decrease with increasing N-siRNA concentrations, reflecting the influence of N-siRNA solutions on surface tension, as indicated by contact angles. These data indicate the utility of APS instruments for investigating the nebulized characteristics of expensive drugs including siRNAs and may facilitate the development of N-siRNA inhalation formulations.Key words small interfering RNA (siRNA); vibrating-mesh nebulizer; aerodynamic particle size; surface tension; contact angle Small interfering RNA (siRNA) has a great therapeutic potential as a tool for the post-transcriptional silencing of target gene expression. 1) Recently, the field of siRNA delivery has rapidly progressed, and the local pulmonary delivery of siRNA has been investigated for various lung diseases. 2,3)Inhalation is the most popular noninvasive method for delivering therapeutic siRNA agents to the lungs 4); local siRNA inhalation therapy reduced virus titers in the lung and attenuated local pulmonary chemokine production after acute lung injury and infection.5,6) However, naked (unmodified) siRNA (N-siRNA) is susceptible to nuclease degradation; siRNA delivery systems facilitating gene silencing efficiency, including those using cationic materials, can have cytotoxic effects. N-siRNA has been delivered with some success to the lung, although systemic delivery of N-siRNA generally fails to produce significant gene silencing effects.3,7) N-siRNA lacks delivery vectors that produce toxicity and inflammation; thus, N-siRNA formulation for pulmonary delivery offers advantages for safety and simplicity. However, few developments of N-siRNA formulations have been reported. Direct pulmonary N-siRNA delivery has been achieved in humans following the inhalation of aerosols generated by inhalers or nebulizers. Three types of inhalation devices are currently available for pulmonary drug delivery, including metered dose inhalers, dry powder inhalers, and nebulizers. Liquid nebulization e...

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Section: Effects Of N-sirna Concentrations and Nebulizer Types On Mmamentioning

confidence: 99%

Inhalation Properties and Stability of Nebulized Naked siRNA Solution for Pulmonary Therapy

2016

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“…CI measurements require sampling the inhaler-produced aerosol and are, therefore, invasive compared with optical-based particle sizing techniques. 4 Although the CI method is complex, 5 it is favored because the masses of active pharmaceutical ingredients (APIs) in each fraction can be specifically assayed. Furthermore, measurements of API are interpreted in terms of particle size aerodynamic diameter, thereby taking into account both particle density and shape.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

2007

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The purpose of this review is to discuss the roles of cascade impactor (CI) data in inhaler assessment and to examine the relationship between aerodynamic particle size distribution (APSD) and the clinical response to inhaled drugs. A systematic literature search of studies linking APSD to clinical response was undertaken. Two distinct roles for CI-generated data were identified: (1) the control of inhaler/drug product quality; and (2) the provision of data that may be predictive of particle deposition in the respiratory tract. Method robustness is required for the former application, combined with simplicity in operation, resulting in rudimentary attempts to mimic the anatomy of the respiratory tract. The latter necessitates making the apparatus and its operation more closely resemble patient use of the inhaler. A CI cannot perfectly simulate the respiratory tract, since it operates at constant flow rate, while the respiratory cycle has a varying flow-time profile. On the basis of a review of studies linking APSD to clinical response of inhaled drugs, it is concluded that attempts to use CIgenerated data from quality control testing to compare products for bioequivalence are likely to have only limited success, as links between laboratory-measured APSD, particle deposition in the respiratory tract, and clinical response are not straightforward.

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“…As an example, one should refer the work of Black et al, Hong et al and Mitchell and Nagel [24][25][26].…”

Section: Experimental Techniquesmentioning

confidence: 99%

pMDI Sprays: Theory, Experiment and Numerical Simulation

Oliveira¹,

Teixeira²,

Teixeira³

et al. 2012

Advances in Modeling of Fluid Dynamics

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Particle Size Analysis of Aerosols from Medicinal Inhalers

Abstract: Methods currently in use for the in-vitro

Cited by 66 publications

References 102 publications

Inhalation Properties and Stability of Nebulized Naked siRNA Solution for Pulmonary Therapy

Inhalation Properties and Stability of Nebulized Naked siRNA Solution for Pulmonary Therapy

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

pMDI Sprays: Theory, Experiment and Numerical Simulation

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