“…Contrary to the results of Duke et al (2021), in which the twin nozzle performed better than the conventional one in terms of drug deposition, our data showed that, in the real MT airway, which influences the distribution of the flow field, the twin nozzle enhanced the drug deposition in only the MT region, rather than deeper parts of the airway. So, according to the present study, not only the higher velocity of aerosol generated by a twin nozzle does not improve the function of pMDI in terms of drug delivery, but it also worsens its efficiency.…”
Section: Discussioncontrasting
confidence: 99%
“…Then, the two plumes collapse before entirely leaving the actuator structure, and one continuous plume appears, like the conventional one. Our result is aligned with that of Duke et al (2021). The spray collapse phenomenon causes a decrease in plume width and an increase in tip penetration (Chang et al 2023;Nishida et al 2009).…”
Section: Plume Behavioursupporting
confidence: 89%
“…Dr. Worth Longest) (Byron et al 2010;Delvadia et al 2012;Delvadia et al 2010;Longest 2008;Xi and Longest 2007) and provided by the RDD Online Respiratory Drug Deliver website (Newman 2015). The geometry of the inhaler nozzles was generated according to Duke et al (2021Duke et al ( ) & (2019; the spray was modelled as an injection of droplets composed of the drug (i.e., ipratropium bromide), the propellant (hydrofluoroalkane (HFA) 134a), and the co-solvent (ethanol). The properties of these components are provided in Table 1.…”
The most commonly used method to deliver aerosolized drugs to the lung is with pressurized metered-dose inhalers (pMDIs). The spray actuator is a critical component of a pMDI, since it controls the atomization process by forming aerosol plumes and determining droplet size distribution. Through computational fluid dynamics (CFD) simulations, this study investigated the effect of two different nozzle types (single conventional and twin nozzles) on drug deposition in the mouth-throat (MT) region. We also studied the behavior of aerosol plumes in both an open-air environment and the MT geometry. Our study revealed that spray aerosol generated in an unconfined, open-air environment with no airflow behaves distinctly from spray introduced into the MT geometry in the presence of airflow. In addition, the actuator structure significantly impacts the device's efficacy. In the real MT airway, we found that the twin nozzle increases drug deposition in the MT region and its higher aerosol velocity negatively affects its efficiency.
“…Contrary to the results of Duke et al (2021), in which the twin nozzle performed better than the conventional one in terms of drug deposition, our data showed that, in the real MT airway, which influences the distribution of the flow field, the twin nozzle enhanced the drug deposition in only the MT region, rather than deeper parts of the airway. So, according to the present study, not only the higher velocity of aerosol generated by a twin nozzle does not improve the function of pMDI in terms of drug delivery, but it also worsens its efficiency.…”
Section: Discussioncontrasting
confidence: 99%
“…Then, the two plumes collapse before entirely leaving the actuator structure, and one continuous plume appears, like the conventional one. Our result is aligned with that of Duke et al (2021). The spray collapse phenomenon causes a decrease in plume width and an increase in tip penetration (Chang et al 2023;Nishida et al 2009).…”
Section: Plume Behavioursupporting
confidence: 89%
“…Dr. Worth Longest) (Byron et al 2010;Delvadia et al 2012;Delvadia et al 2010;Longest 2008;Xi and Longest 2007) and provided by the RDD Online Respiratory Drug Deliver website (Newman 2015). The geometry of the inhaler nozzles was generated according to Duke et al (2021Duke et al ( ) & (2019; the spray was modelled as an injection of droplets composed of the drug (i.e., ipratropium bromide), the propellant (hydrofluoroalkane (HFA) 134a), and the co-solvent (ethanol). The properties of these components are provided in Table 1.…”
The most commonly used method to deliver aerosolized drugs to the lung is with pressurized metered-dose inhalers (pMDIs). The spray actuator is a critical component of a pMDI, since it controls the atomization process by forming aerosol plumes and determining droplet size distribution. Through computational fluid dynamics (CFD) simulations, this study investigated the effect of two different nozzle types (single conventional and twin nozzles) on drug deposition in the mouth-throat (MT) region. We also studied the behavior of aerosol plumes in both an open-air environment and the MT geometry. Our study revealed that spray aerosol generated in an unconfined, open-air environment with no airflow behaves distinctly from spray introduced into the MT geometry in the presence of airflow. In addition, the actuator structure significantly impacts the device's efficacy. In the real MT airway, we found that the twin nozzle increases drug deposition in the MT region and its higher aerosol velocity negatively affects its efficiency.
“…Data propose that smaller orifices (0.22 mm) generate fine particles and higher sustained plume velocities cause higher fine particles at the periphery of the spray owing to improved shear. A small change in the pMDI device significantly impacts the drug deposition profile and improves formulation aerodynamic functioning ( 113 ). Fig.…”
“…Duke et al . [ 46 ] have reported that decreasing the spray orifice diameter has the effect of increasing both the plume velocity and fine particle fraction keeping the vapor pressure of the pMDI formulation constant [ 46 ]. In the case of DPIs, one of the major device parameters that can affect the fine particle fraction is the internal mesh design that is primarily responsible for the device resistance that needs to be overcome by the patient’s inhalation flow rate in order to enable optimal de-aggregation of the API drug particles from the lactose carrier.…”
The COVID-19 pandemic has proven to be an unprecedented health crisis in the human history with more than 5 million deaths worldwide caused to the SARS-CoV-2 and its variants (
https://www.who.int/emergencies/diseases/novel-coronavirus-2019
). The currently authorized lipid nanoparticle (LNP)–encapsulated mRNA vaccines have been shown to have more than 90% vaccine efficacy at preventing COVID-19 illness (Baden
et al
. New England J Med 384(5):403–416,
2021
; Thomas
et al
.,
2021
). In addition to vaccines, other small molecules belonging to the class of anti-viral and anti-inflammatory compounds have also been prescribed to reduce the viral proliferation and the associated cytokine storm. These anti-viral and anti-inflammatory compounds have also been shown to be effective in reducing COVID-19 exacerbations especially in reducing the host inflammatory response to SARS-CoV-2. However, all of the currently FDA-authorized vaccines for COVID-19 are meant for intramuscular injection directly into the systemic circulation. Also, most of the small molecules investigated for their anti-COVID-19 efficacy have also been explored using the intravenous route with a few of them explored for the inhalation route (Ramakrishnan
et al
. Lancet Respir Med 9:763–772,
2021
; Horby
et al
. N Engl J Med 384(8):693–704,
2021
). The fact that the SARS-CoV-2 enters the human body mainly via the nasal and airway route resulting in the lungs being the primary organs of infection as characterized by acute respiratory distress syndrome (ARDS)–mediated cytokine storm in the alveolar region has made the inhalation route gain significant attention for the purposes of targeting both vaccines and small molecules to the lungs (Mitchell
et al
., J Aerosol Med Pulm Drug Deliv 33(4):235–8,
2020
). While there have been many studies reporting the safety and efficacy of targeting various therapeutics to the lungs to treat COVID-19, there is still a need to match the choice of inhalation formulation and the delivery device platform itself with the patient-related factors like breathing pattern and respiratory rate as seen in a clinical setting. In that perspective, this review aims to describe the various formulation and patient-related clinical factors that can play an important role in the judicious choice of the inhalation delivery platforms or devices for the development of inhaled COVID-19 vaccines.
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