Development of a High-Dose Infant Air-Jet Dry Powder Inhaler (DPI) with Passive Cyclic Loading of the Formulation

Howe, Connor A.; Momin, Mohammad A.M.; Aladwani, Ghali; Hindle, Michael; Longest, P. Worth

doi:10.1007/s11095-022-03409-5

Cited by 5 publications

(3 citation statements)

References 45 publications

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“…A curved nasal prong was connected to the outlet of the GE and RE to direct the aerosol into the infant's nose. Further details on aerosol delivery to infants using the D2I approach are provided elsewhere ( Howe et al, 2022a , 2022b ).…”

Section: Methodsmentioning

confidence: 99%

“…In this study the EIM modifications include use of interpolated fluctuation velocity and TKE, a lower limit on eddy lifetime, and a drift correction term ( Bocksell & Loth, 2001 , 2006 ; Mofakham & Ahmadi, 2020 ). The pharmaceutical aerosol system selected is an air-jet DPI ( Farkas et al, 2018a ; Farkas et al, 2018b ) for administering small-particle aerosols to infants ( Bass, Boc, et al, 2019 ; Howe et al, 2022a , 2022b ) via the nose-to-lung (N2L) route. To ensure that deposition mechanisms are accurately captured across a range of turbulence levels, additional benchmark systems are also considered, including a curved tube (deposition due to impaction enhanced by turbulent dispersion) and a vertical straight pipe (dispersion due purely to turbulent dispersion).…”

Section: Introductionmentioning

confidence: 99%

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Development of an effective two-equation turbulence modeling approach for simulating aerosol deposition across a range of turbulence levels

Jubaer,

Thomas,

Farkas

et al. 2024

Journal of Aerosol Science

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of an effective two-equation turbulence modeling approach for simulating aerosol deposition across a range of turbulence levels

Jubaer,

Thomas,

Farkas

et al. 2024

Journal of Aerosol Science

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“…The percentage of albuterol EEG aerosol powder retained in the Rat AJ DPI at 1, 2, and 5 mg loading mass was determined using a high-performance liquid chromatography (HPLC) method adapted from Howe et al 23 In brief, the powder mass recovered from the device was dissolved in an appropriate volume of deionized water and analyzed by HPLC with a fluorescence detector (ex/em: 276/609 nm). Chromatographic separation was achieved using a Restek Allure PFP propyl column (5 μm, 60 Å, 150 × 2.1 mm) and a mobile phase composition of methanol and ammonium formate buffer (20 mM, pH 3.4 through addition of formic acid) in a ratio of 70:30, run at a flow rate of 0.4 mL/min.…”

Section: Small-animal Air-jet Dry Powder Insufflator (Rat Aj Dpi) The...mentioning

confidence: 99%

New Air-Jet Dry Powder Insufflator for High-Efficiency Aerosol Delivery to Rats

et al. 2023

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Pulmonary deposition of lung-targeted therapeutic aerosols can achieve direct drug delivery to the site of action, thereby enhancing the efficacy and reducing systemic exposure. In this study, we investigated the in vitro and in vivo aerosol performance of the novel small animal air-jet dry powder insufflator (Rat AJ DPI) using spray-dried albuterol excipient-enhancedgrowth (EEG) powder as a model formulation. The in vitro aerosolization performance of the optimized albuterol EEG powder was first assessed using the Rat AJ DPI. The performance of Rat AJ DPI to deliver albuterol EEG aerosol to rat lungs was then compared to that of the Penn-Century Insufflator. Albuterol EEG powders dispersed using the Rat AJ DPI demonstrated narrow unimodal aerosol size distribution profiles, which were independent of the loaded powder dose (1, 2, and 5 mg). In addition, the span value for Rat AJ DPI (5 mg powder mass) was 1.32, which was 4.2fold lower than that for Penn-Century insufflator (5 mg powder mass). At a higher loaded mass of 5 mg, the Rat AJ DPI delivered significantly larger doses to rat lungs compared with the Penn-Century DPI. The Rat AJ DPI with hand actuation delivered approximately 85% of the total emitted dose (2 and 5 mg loadings), which was comparatively higher than that for Penn-Century DPI (approximately 75%). In addition, percentage deposition in each of the lung lobes for the Rat AJ DPI was observed to be independent of the administration dose (2 and 5 mg loadings) with coefficients of variation below 12%, except in the right middle lobe. Automatic actuation of a 5 mg powder mass using the Rat AJ DPI demonstrated a similar delivered dose compared to manual actuation of the same dose, with 82% of the total emitted dose reaching the lung lobes. High-efficiency delivery of the aerosol to the lobar lung region and low sensitivity of the interlobar delivery efficiency to the loaded dose highlight the suitability of the new air-jet DPI for administering therapeutic pharmaceutical aerosols to small test animals.

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Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) – Part I: In Vitro Testing and Characterization

Momin,

Farkas,

Hindle

et al. 2024

Pharm Res

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Purpose Improving the deep lung delivery of aerosol surfactant therapy (AST) with a dry powder formulation may enable significant reductions in dose while providing improved efficacy. The objective of Part I of this two-part study was to present the development of a new dry powder aerosol synthetic lung surfactant (SLS) product and to characterize performance based on aerosol formation and realistic in vitro airway testing leading to aerosol delivery recommendations for subsequent in vivo animal model experiments. Methods A new micrometer-sized SLS excipient enhanced growth (EEG) dry powder formulation was produced via spray drying and aerosolized using a positive-pressure air-jet dry powder inhaler (DPI) intended for aerosol delivery directly to intubated infants with respiratory distress syndrome (RDS) or infant-size test animals. Results The best-case design (D2) of the air-jet DPI was capable of high emitted dose (> 80% of loaded) and formed a < 2 µm mass median aerodynamic diameter (MMAD) aerosol, but was limited to ≤ 20 mg mass loadings. Testing with a realistic in vitro rabbit model indicated that over half of the loaded dose could penetrate into the lower lung regions. Using the characterization data, a dose delivery protocol was designed in which a 60 mg total loaded dose would be administered and deliver an approximate lung dose of 14.7–17.7 mg phospholipids/kg with a total aerosol delivery period < 5 min. Conclusions A high-efficiency aerosol SLS product was designed and tested that may enable an order of magnitude reduction in administered phospholipid dose, and provide rapid aerosol administration to infants with RDS.

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Development of a High-Dose Infant Air-Jet Dry Powder Inhaler (DPI) with Passive Cyclic Loading of the Formulation

Cited by 5 publications

References 45 publications

Development of an effective two-equation turbulence modeling approach for simulating aerosol deposition across a range of turbulence levels

Development of an effective two-equation turbulence modeling approach for simulating aerosol deposition across a range of turbulence levels

New Air-Jet Dry Powder Insufflator for High-Efficiency Aerosol Delivery to Rats

Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) – Part I: In Vitro Testing and Characterization

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