Pharmaceutical Aerosols and Pulmonary Drug Delivery

Murnane, Darragh; Hutter, Victoria; Harang, Marie

doi:10.1002/9781118682555.ch10

Cited by 4 publications

(4 citation statements)

References 214 publications

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“…The concept of nasal pMDIs was introduced for the treatment of allergic rhinitis to overcome the limitations of aqueous pump sprays, including the loss of formulation by running down the throat or dripping from the nose and the resulting unpleasant taste and burning sensation, which limited the delivered dose and patient compliance. From a deposition perspective, pMDIs generate much smaller droplet sizes (≤5 µm) than aqueous nasal sprays, where larger particles are expected to develop inertial impaction in the nasal anterior vestibule and nasopharynx [52][53][54], whereas smaller particles (0.5-5 µm) are expected to travel further down to the lower respiratory tract [55]. The possibility of enhancing the deposition of ultra-small particles in the posterior region of the nasal cavity, where the olfactory region is located, for NTBDD utilizing a pMDI device has not yet been well investigated in vitro.…”

Section: Regional Nasal Deposition Of Aerosolized Gnusmentioning

confidence: 99%

“…terior vestibule and nasopharynx [52][53][54], whereas smaller particles (0.5-5 µm) are expected to travel further down to the lower respiratory tract [55]. The possibility of enhancing the deposition of ultra-small particles in the posterior region of the nasal cavity, where the olfactory region is located, for NTBDD utilizing a pMDI device has not yet been well investigated in vitro.…”

Section: Regional Nasal Deposition Of Aerosolized Gnusmentioning

confidence: 99%

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Gold Nanoparticles: Tunable Characteristics and Potential for Nasal Drug Delivery

Maaz,

Blagbrough,

De Bank

2024

Pharmaceutics

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A general procedure to prepare gold nanourchins (GNUs) via a seed-mediated method was followed using dopamine hydrochloride as a reducing agent and silver nitrate salt (AgNO3) as a shape-directing agent. The novelty of this study comes from the successful incorporation of the prepared gold urchins as an aqueous suspension in a nasal pressurized metered dose inhaler (pMDI) formulation and the investigation of their potential for olfactory targeting for direct nose-to-brain drug delivery (NTBDD). The developed pMDI formulation was composed of 0.025% w/w GNUs, 2% w/w Milli-Q water, and 2% w/w EtOH, with the balance of the formulation being HFA134a propellant. Particle integrity and aerosolization performance were examined using an aerosol exposure system, whereas the nasal deposition profile was tested in a sectioned anatomical replica of human nasal airways. The compatibility of the gold dispersion with the nasal epithelial cell line RPMI 2650 was also investigated in this study. Colloidal gold was found to be stable following six-month storage at 4 °C and during the lyophilization process utilizing a pectin matrix for complete re-dispersibility in water. The GNUs were intact and discrete following atomization via a pMDI, and 13% of the delivered particles were detected beyond the nasal valve, the narrowest region in the nasal cavity, out of which 5.6% was recovered from the olfactory region. Moreover, the formulation was found to be compatible with the human nasal epithelium cell line RPMI 2650 and excellent cell viability was observed. The formulated GNU-HFA-based pMDI is a promising approach for intranasal drug delivery, including deposition in the olfactory region, which could be employed for NTBDD applications.

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Section: Regional Nasal Deposition Of Aerosolized Gnusmentioning

confidence: 99%

Section: Regional Nasal Deposition Of Aerosolized Gnusmentioning

confidence: 99%

Gold Nanoparticles: Tunable Characteristics and Potential for Nasal Drug Delivery

Maaz,

Blagbrough,

De Bank

2024

Pharmaceutics

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“…Particles of high MMAD inhaled at high velocity are deposited in the airway bifurcation by impaction, while smaller particles are deposited deeper in the lungs (i.e., in the small airway) by sedimentation and impaction. Periods of breath-holding can enhance the deposition by the latter two mechanisms as they allow more time for particles with low settling velocity to deposit [2]. It is often stated that due to their low settling velocity, submicron particles are exhaled.…”

Section: Pulmonary Drug Delivery Using Dry Powder Inhalersmentioning

confidence: 99%

Spray Drying for the Preparation of Nanoparticle-Based Drug Formulations as Dry Powders for Inhalation

Malamatari¹,

et al. 2020

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Nanoparticle-based therapeutics have been used in pulmonary formulations to enhance delivery of poorly water-soluble drugs, protect drugs against degradation and achieve modified release and drug targeting. This review focuses on the use of spray drying as a solidification technique to produce microparticles containing nanoparticles (i.e., nanoparticle (NP) agglomerates) with suitable properties as dry powders for inhalation. The review covers the general aspects of pulmonary drug delivery with emphasis on nanoparticle-based dry powders for inhalation and the principles of spray drying as a method for the conversion of nanosuspensions to microparticles. The production and therapeutic applications of the following types of NP agglomerates are presented: nanoporous microparticles, nanocrystalline agglomerates, lipid-based and polymeric formulations. The use of alternative spray-drying techniques, namely nano spray drying, and supercritical CO2-assisted spray drying is also discussed as a way to produce inhalable NP agglomerates.

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“…The effectiveness of a pMDI is directly dependent on its capability to produce drug aerosol particles that reach, and are deposited in, the target region of the respiratory system to instigate therapeutic effect [ 7 ]. It is generally accepted that for effective pulmonary deposition, aerosol particle sizes must be 1–5 µm in diameter: larger particles will impact in the oropharynx and smaller particles have insufficient inertia for deposition [ 8 ]. Consequently, there has been significant research into the accurate measurement and prediction of pMDI aerosol generation and sizing.…”

Section: Introductionmentioning

confidence: 99%

Water Uptake by Evaporating pMDI Aerosol Prior to Inhalation Affects Both Regional and Total Deposition in the Respiratory System

et al. 2021

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As pulmonary drug deposition is a function of aerosol particle size distribution, it is critical that the dynamics of particle formation and maturation in pMDI sprays in the interim between generation and inhalation are fully understood. This paper presents an approach to measure the evaporative and condensational fluxes of volatile components and water from and to solution pMDI droplets following generation using a novel technique referred to as the Single Particle Electrodynamic Lung (SPEL). In doing so, evaporating aerosol droplets are shown capable of acting as condensation nuclei for water. Indeed, we show that the rapid vaporisation of volatile components from a volatile droplet is directly correlated to the volume of water taken up by condensation. Furthermore, a significant volume of water is shown to condense on droplets of a model pMDI formulation (hydrofluoroalkane (HFA), ethanol and glycerol) during evaporative droplet ageing, displaying a dramatic shift from a core composition of a volatile species to that of predominantly water (non-volatile glycerol remained in this case). This yields a droplet with a water activity of 0.98 at the instance of inhalation. The implications of these results on regional and total pulmonary drug deposition are explored using the International Commission of Radiological Protection (ICRP) deposition model, with an integrated semi-analytical treatment of hygroscopic growth. Through this, droplets with water activity of 0.98 upon inhalation are shown to produce markedly different dose deposition profiles to those with lower water activities at the point of inspiration.

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Pharmaceutical Aerosols and Pulmonary Drug Delivery

Cited by 4 publications

References 214 publications

Gold Nanoparticles: Tunable Characteristics and Potential for Nasal Drug Delivery

Gold Nanoparticles: Tunable Characteristics and Potential for Nasal Drug Delivery

Spray Drying for the Preparation of Nanoparticle-Based Drug Formulations as Dry Powders for Inhalation

Water Uptake by Evaporating pMDI Aerosol Prior to Inhalation Affects Both Regional and Total Deposition in the Respiratory System

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